CA2709379C - Hydrogel filaments for biomedical uses - Google Patents
Hydrogel filaments for biomedical uses Download PDFInfo
- Publication number
- CA2709379C CA2709379C CA2709379A CA2709379A CA2709379C CA 2709379 C CA2709379 C CA 2709379C CA 2709379 A CA2709379 A CA 2709379A CA 2709379 A CA2709379 A CA 2709379A CA 2709379 C CA2709379 C CA 2709379C
- Authority
- CA
- Canada
- Prior art keywords
- hydrogel
- ethylenically unsaturated
- macromer
- combinations
- unsaturated monomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000017 hydrogel Substances 0.000 title claims abstract description 147
- 239000000178 monomer Substances 0.000 claims abstract description 54
- 238000002513 implantation Methods 0.000 claims abstract description 17
- 241001465754 Metazoa Species 0.000 claims abstract description 5
- -1 poly(tetramethylene oxide) Polymers 0.000 claims description 43
- 238000012800 visualization Methods 0.000 claims description 34
- 239000003795 chemical substances by application Substances 0.000 claims description 30
- 229920001223 polyethylene glycol Polymers 0.000 claims description 16
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 11
- 125000000524 functional group Chemical group 0.000 claims description 11
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- CHDKQNHKDMEASZ-UHFFFAOYSA-N n-prop-2-enoylprop-2-enamide Chemical compound C=CC(=O)NC(=O)C=C CHDKQNHKDMEASZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 6
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 6
- ICBOHMPCHYQPDI-UHFFFAOYSA-N (2,4,6-triiodophenyl) pent-4-enoate Chemical compound IC1=CC(I)=C(OC(=O)CCC=C)C(I)=C1 ICBOHMPCHYQPDI-UHFFFAOYSA-N 0.000 claims description 5
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 5
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 5
- 229910001938 gadolinium oxide Inorganic materials 0.000 claims description 5
- 229940075613 gadolinium oxide Drugs 0.000 claims description 5
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- LXEKPEMOWBOYRF-UHFFFAOYSA-N [2-[(1-azaniumyl-1-imino-2-methylpropan-2-yl)diazenyl]-2-methylpropanimidoyl]azanium;dichloride Chemical compound Cl.Cl.NC(=N)C(C)(C)N=NC(C)(C)C(N)=N LXEKPEMOWBOYRF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical class C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 3
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 3
- 125000004386 diacrylate group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 23
- 230000036244 malformation Effects 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 5
- 230000003111 delayed effect Effects 0.000 abstract description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 82
- 239000000243 solution Substances 0.000 description 64
- 229910052697 platinum Inorganic materials 0.000 description 41
- 206010002329 Aneurysm Diseases 0.000 description 25
- 239000002904 solvent Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 229920000642 polymer Polymers 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 230000003073 embolic effect Effects 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000945 filler Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229910052788 barium Inorganic materials 0.000 description 6
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000002843 carboxylic acid group Chemical group 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 241000158500 Platanus racemosa Species 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 230000010102 embolization Effects 0.000 description 4
- 238000002594 fluoroscopy Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000003739 neck Anatomy 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 238000005452 bending Methods 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910052715 tantalum Inorganic materials 0.000 description 3
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000018152 Cerebral disease Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 238000002583 angiography Methods 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008238 biochemical pathway Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 1
- VAPDZNUFNKUROY-UHFFFAOYSA-N 2,4,6-triiodophenol Chemical compound OC1=C(I)C=C(I)C=C1I VAPDZNUFNKUROY-UHFFFAOYSA-N 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940048053 acrylate Drugs 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- OTTYFDRFBJPGRW-UHFFFAOYSA-N pent-2-enoyl chloride Chemical compound CCC=CC(Cl)=O OTTYFDRFBJPGRW-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229940047670 sodium acrylate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- SONHXMAHPHADTF-UHFFFAOYSA-M sodium;2-methylprop-2-enoate Chemical compound [Na+].CC(=C)C([O-])=O SONHXMAHPHADTF-UHFFFAOYSA-M 0.000 description 1
- 238000005476 soldering Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
- A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
- A61B17/12113—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel within an aneurysm
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
- A61B17/12181—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0404—X-ray contrast preparations containing barium sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/18—Materials at least partially X-ray or laser opaque
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00004—(bio)absorbable, (bio)resorbable or resorptive
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B2017/1205—Introduction devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
- A61B2090/3966—Radiopaque markers visible in an X-ray image
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/36—Materials or treatment for tissue regeneration for embolization or occlusion, e.g. vaso-occlusive compositions or devices
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dispersion Chemistry (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Reproductive Health (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Surgical Instruments (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
Described herein are apparatus, compositions, systems and associated methods to occlude structures and malformations with radiopaque hydrogel filaments with delayed controlled rates of expansion permitting the repositioning of the device once inside the structure or malformation. Further described is a device for implantation in an animal comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a radiopaque element, wherein said device contains no support members. Methods of forming such devices are also disclosed.
Description
HYDROGEL FILAMENTS FOR BIOMEDICAL USES
[0001]
FIELD OF THE INVENTION
[0001]
FIELD OF THE INVENTION
[0002]
The present invention relates generally to medical treatment apparatus and methods, more particularly, hydrogel filaments visible under x-ray fluoroscopy = and magnetic resonance, and methods for use of such materials in biomedical treatment.
BACKGROUND
=
The present invention relates generally to medical treatment apparatus and methods, more particularly, hydrogel filaments visible under x-ray fluoroscopy = and magnetic resonance, and methods for use of such materials in biomedical treatment.
BACKGROUND
=
[0003]
Presently, for patients suffering from cerebral and/or peripheral vascular disease, an interventional neuroradiologist/neurosurgeon has three main embolic device choices:
platinum coils, hydrogel/platinum coils, or degradable = polymer/platinum coils. All three types of coils are deployed into aneurysms and have advantages and disadvantages associated with them. Platinum coils are easy to deploy through standard microcatheters, are available in wide ranges of softness, and are best suited for aneurysms with small sizes or necks. Hydrogel/platinum coils are also easy to deploy through standard microcatheters. Although hydrogel/platinum coils are relatively stiffer than platinum coils and can be challenging to deploy inside aneurysms, they give acceptable results in a broader range of sac and neck sizes. Degradable polymer/platinum coils are easily tracked and deployed into aneurysm sacs; however, they only give acceptable results in aneurysms with small sizes or necks.
=
Presently, for patients suffering from cerebral and/or peripheral vascular disease, an interventional neuroradiologist/neurosurgeon has three main embolic device choices:
platinum coils, hydrogel/platinum coils, or degradable = polymer/platinum coils. All three types of coils are deployed into aneurysms and have advantages and disadvantages associated with them. Platinum coils are easy to deploy through standard microcatheters, are available in wide ranges of softness, and are best suited for aneurysms with small sizes or necks. Hydrogel/platinum coils are also easy to deploy through standard microcatheters. Although hydrogel/platinum coils are relatively stiffer than platinum coils and can be challenging to deploy inside aneurysms, they give acceptable results in a broader range of sac and neck sizes. Degradable polymer/platinum coils are easily tracked and deployed into aneurysm sacs; however, they only give acceptable results in aneurysms with small sizes or necks.
=
[0004]
Despite the three coil varieties, there exists an unmet clinical need for embolic devices that deploy easily into aneurysm sacs (like platinum coils) and result in durable occlusion in a wide variety of aneurysm sizes (like hydrogel/platinum coils). Among the benefits of the apparatus and methods of the present description [PCT/US2008/087846 n 195(3 ibb-UUU07 is a device that tracks through a microcatheter with less friction than a platinum coil, deploys in the aneurysm sac like the softest platinum coil on the market, expands like the hydrogel/platinum coils, and provides durable occlusion of the aneurysm sac, while permitting the interventional neuroradiologist/neurosurgeon, or surgeon, to use standard microcatheters and other associated equipment.
Despite the three coil varieties, there exists an unmet clinical need for embolic devices that deploy easily into aneurysm sacs (like platinum coils) and result in durable occlusion in a wide variety of aneurysm sizes (like hydrogel/platinum coils). Among the benefits of the apparatus and methods of the present description [PCT/US2008/087846 n 195(3 ibb-UUU07 is a device that tracks through a microcatheter with less friction than a platinum coil, deploys in the aneurysm sac like the softest platinum coil on the market, expands like the hydrogel/platinum coils, and provides durable occlusion of the aneurysm sac, while permitting the interventional neuroradiologist/neurosurgeon, or surgeon, to use standard microcatheters and other associated equipment.
[0005] The improved durability of hydrogel/platinum coils is believed to be a result of the increased volumetric filling of the aneurysm sac and the resulting increase in stability of the coil mass. A current version of the hydrogel/platinum coil has an overcoil which limits the expansion of the hydrogel. In preclinical models, while current overcoiled hydrogel/platinum coils provide better results than platinum coils, it is believed that a non-overcoiled hydrogel device would be less stiff than current overcoiled versions. The present description provides an embolic device that is capable of providing increased volumetric filling, more so than both platinum coils and overcoiled hydrogel/platinum coils, with less stiffness than overcoiled hydrogel/platinum coils.
[0006] In large and giant aneurysms, inflammatory complications can occur, presumably due to the large amount of thrombus formation and organization. It is believed that with the increased volumetric filling of the aneurysm sac provided by the hydrogel, decreased thrombus formation and organization occurs and presumably fewer inflammatory complications result. The present description provides an embolic device which could reduce inflammatory complications.
[0007] An uncommon, but potentially dangerous, complication occurs when a coil gets interlocked within the winds of the coil itself. In this case, one can neither push nor pull the coil while keeping the device intact within the aneurysm site.
The only option is to pull back and unwind the coil from the aneurysm site to the groin. The potentially dangerous result is a stretched coil. Although stretch resistant coils have been developed, this complication has not been eliminated, and still poses a dangerous threat to a patient. It is believed that the device of the present description eliminates this complication altogether.
The only option is to pull back and unwind the coil from the aneurysm site to the groin. The potentially dangerous result is a stretched coil. Although stretch resistant coils have been developed, this complication has not been eliminated, and still poses a dangerous threat to a patient. It is believed that the device of the present description eliminates this complication altogether.
8 [PCT/US2008/087846 n 195(3 /t3b-UUU07 SUMMARY
[0008]
Described herein are apparatuses, compositions, systems and associated methods to occlude structures and malformations in body lumens with hydrogel filaments with delayed controlled rates of expansion including one or more visualization agents permitting the repositioning of the device once inside the structure or malformation. The structures and malformations can be a result of any number of cerebral and/or peripheral diseases. Generally, the controlled rate of expansion is imparted through the incorporation of ethylenically unsaturated monomers with ionizable functional groups, (e.g. amines, carboxylic acids).
For example, if acrylic acid is incorporated into the cross-linked polymeric network, the hydrogel is then incubated in a low pH solution to protonate the carboxylic acids.
After the excess low pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the carboxylic acid groups deprotonate. Conversely, if an amine-containing monomer is incorporated into the cross-linked network, the hydrogel is incubated in a high pH solution to deprotonate amines. After the excess high pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the amine groups protonate.
[0008]
Described herein are apparatuses, compositions, systems and associated methods to occlude structures and malformations in body lumens with hydrogel filaments with delayed controlled rates of expansion including one or more visualization agents permitting the repositioning of the device once inside the structure or malformation. The structures and malformations can be a result of any number of cerebral and/or peripheral diseases. Generally, the controlled rate of expansion is imparted through the incorporation of ethylenically unsaturated monomers with ionizable functional groups, (e.g. amines, carboxylic acids).
For example, if acrylic acid is incorporated into the cross-linked polymeric network, the hydrogel is then incubated in a low pH solution to protonate the carboxylic acids.
After the excess low pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the carboxylic acid groups deprotonate. Conversely, if an amine-containing monomer is incorporated into the cross-linked network, the hydrogel is incubated in a high pH solution to deprotonate amines. After the excess high pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the amine groups protonate.
[0009] In one embodiment described herein is a device for implantation comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a visualization agent, wherein the device contains no support members. In one embodiment, the support members are metallic.
[0010] In one embodiment, the macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole. In another embodiment, the hydrogel is environmentally-responsive. In yet another embodiment, the ethylenically unsaturated monomer comprises one or more ionizable functional groups.
[0011] In one embodiment, the macromer comprises polyethylene glycol, propylene glycol, poly(tetramethylene oxide), poly(ethylene glycol) diacrylamide, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, derivatives [PCT/US2008/087846 n 195(3 ibb-UUU07 thereof, or combinations thereof. In another embodiment, the ethylenically unsaturated monomer comprises N,N'-methylenebisacrylamide, N-vinyl pyrrolidinone, 2-hydroxyethyl methacrylate, derivatives thereof, or combinations thereof.
[0012] In one embodiment, the visualization agents include radiopaque elements comprising an aromatic ring having a single unsaturation point and at least one iodine atom, tantalum, barium, salts thereof, or combinations thereof. In one embodiment, the visualization agent an aromatic ring having a single unsaturation point and two iodine atoms. In one embodiment, the visualization agent comprises gadolinium or iron oxide to impart visibility under magnetic resonance imaging.
[0013] In one embodiment, the ethylenically unsaturated monomer and the visualization agent comprise 2,4,6-triiodophenyl penta-4-enoate, 5-acrylamido-2,4,6-triiodo-n,n'-bis-(2,3 dihydroxypropyl) isophthalamide, derivatives thereof, or combinations thereof.
[0014] In one embodiment, the polymerization of the macromer and the monomer is initiated by N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2'-azobis(2-methylpropionamidine) dihydrochloride, derivatives thereof, or combinations thereof.
[0015] In one embodiment, the ionizable functional groups comprise acidic groups or basic groups. In one embodiment, the basic group comprises amine groups, derivatives thereof, or combinations thereof. In another embodiment, the acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.
[0016] In one embodiment, the hydrogel is substantially free of acrylamide. In another embodiment, the hydrogel is substantially non-bioresorbable. In another embodiment, the hydrogel is bioresorbable.
[0017] One embodiment described herein is a method for preparing a device for implantation in an animal comprising: a) combining a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; a visualization agent, and a solvent to prepare a prepolymer solution; and b) treating the prepolymer solution to prepare a hydrogel that is expansible at physiological conditions.
= CA 02709379 2015-08-12
= CA 02709379 2015-08-12
[0018]
In one embodiment of the method, the solvent comprises water, dichloromethane, acetone, isopropyl alcohol, ethanol, or combinations thereof.
In another embodiment, the difunctional, low molecular weight ethylenically unsaturated shapeable macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.
In yet another embodiment, the ethylenically unsaturated = monomer comprises ionizable functional groups.
In one embodiment of the method, the solvent comprises water, dichloromethane, acetone, isopropyl alcohol, ethanol, or combinations thereof.
In another embodiment, the difunctional, low molecular weight ethylenically unsaturated shapeable macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.
In yet another embodiment, the ethylenically unsaturated = monomer comprises ionizable functional groups.
[0019]
In one embodiment of the method, solvent comprises about 20% w/w to about 80% w/w of the prepolymer solution. In another embodiment, the monomer =
comprises about 40% to about 80% by weight of the prepolymer solution.
In one embodiment of the method, solvent comprises about 20% w/w to about 80% w/w of the prepolymer solution. In another embodiment, the monomer =
comprises about 40% to about 80% by weight of the prepolymer solution.
[0020]
In one embodiment, the method further comprises the step of adding a second an ethylenically unsaturated monomer to the prepolymer solution.
In one embodiment, the method further comprises the step of adding a second an ethylenically unsaturated monomer to the prepolymer solution.
[0021]
In one embodiment of the method, the ionizable functional groups comprise basic groups and the treating step comprises de-protonating the basic groups at pHs greater than the pKa or protonating the basic groups at pHs less than the pKa of the basic groups. In another embodiment of the method, the ionizable functional groups comprise acidic groups and the treating step comprises protonating the acidic groups at pHs less than the pKa or de-protonating the acidic = groups at pHs greater than the pKa of said acidic groups.
In one embodiment of the method, the ionizable functional groups comprise basic groups and the treating step comprises de-protonating the basic groups at pHs greater than the pKa or protonating the basic groups at pHs less than the pKa of the basic groups. In another embodiment of the method, the ionizable functional groups comprise acidic groups and the treating step comprises protonating the acidic groups at pHs less than the pKa or de-protonating the acidic = groups at pHs greater than the pKa of said acidic groups.
[0022]
In another embodiment, a device is described for implantation comprising:
a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole; an ethylenically unsaturated monomer; and a visualization agent, wherein the device contains no metallic support members.
[0022a] In one claimed aspect, the invention relates to a device for implantation comprising: a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 0.4 gf.
[002213] In a further claimed aspect, the invention relates to a device for implantation in an animal comprising: a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole; an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 0.4 gf.
DETAILED DESCRIPTION
In another embodiment, a device is described for implantation comprising:
a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole; an ethylenically unsaturated monomer; and a visualization agent, wherein the device contains no metallic support members.
[0022a] In one claimed aspect, the invention relates to a device for implantation comprising: a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 0.4 gf.
[002213] In a further claimed aspect, the invention relates to a device for implantation in an animal comprising: a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole; an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 0.4 gf.
DETAILED DESCRIPTION
[0023] Described herein are apparatuses, compositions, systems and associated methods for occluding structures and malformations resulting from one or more cerebral and/or peripheral vascular diseases. Hydrogel filaments comprising one or more visualization agents having delayed, controlled rates of expansion are used to treat these structures and malformations, thereby permitting the repositioning of the device once inside the structure or malformation. Further, the hydrogel filaments including one or more visualization agents, for example radiopaque elements or fillers, with controlled rates of expansion give a surgeon a sufficient . amount of time 5a [PCT/US2008/087846 n to properly position the filament without the need to rush as a result of immediate filament expansion.
[0024]
Generally, the controlled rate of expansion of the hydrogel filaments is imparted through the incorporation of ethylenically unsaturated monomers with ionizable functional groups, (e.g. acidic or basic groups). For example, if acrylic acid is incorporated into the cross-linked polymeric network, the hydrogel is incubated in a low pH solution to protonate acidic, carboxylic acids. After the excess low pH
solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH.
The hydrogel cannot and will not expand until the carboxylic acid groups deprotonate. Conversely, if a basic, amine containing monomer is incorporated into the cross-linked network, the hydrogel is incubated in a high pH solution to deprotonate amines. After the excess high pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the amine groups are protonated.
Generally, the controlled rate of expansion of the hydrogel filaments is imparted through the incorporation of ethylenically unsaturated monomers with ionizable functional groups, (e.g. acidic or basic groups). For example, if acrylic acid is incorporated into the cross-linked polymeric network, the hydrogel is incubated in a low pH solution to protonate acidic, carboxylic acids. After the excess low pH
solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH.
The hydrogel cannot and will not expand until the carboxylic acid groups deprotonate. Conversely, if a basic, amine containing monomer is incorporated into the cross-linked network, the hydrogel is incubated in a high pH solution to deprotonate amines. After the excess high pH solution has been rinsed away and the hydrogel dried, the hydrogel can be introduced through a microcatheter filled with blood or saline at physiological pH. The hydrogel cannot and will not expand until the amine groups are protonated.
[0025] In one embodiment, whether acidic or basic groups are utilized on the monomeric species according to the present description, the devices described herein are expansible at physiological conditions. Physiological condition as used herein means a condition having at least one environmental characteristic found within or on the human body. Such characteristics include isotonic environment, pH
buffered environment, aqueous environment, a pH of about 7, or combinations thereof and can be found in, for example, an isotonic solution, water, blood, spinal fluid, plasma, serum, vitreous humor or urine.
buffered environment, aqueous environment, a pH of about 7, or combinations thereof and can be found in, for example, an isotonic solution, water, blood, spinal fluid, plasma, serum, vitreous humor or urine.
[0026] In one embodiment generally described herein are devices for implantation comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a visualization element, wherein the device contains no support members. In one embodiment, the device contains one or more support members, but those support members are not metallic.
Non-metallic support members can be polymeric. In one embodiment, the devices have one or more non-radiopaque or visualizable support members. In some embodiments, support members are not needed in the devices described herein to [PCT/US2008/087846 n 195(3 ibb-UUU07 control expansion of the hydrogel, and as such, they are not incorporated into the apparatus and systems described herein.
Non-metallic support members can be polymeric. In one embodiment, the devices have one or more non-radiopaque or visualizable support members. In some embodiments, support members are not needed in the devices described herein to [PCT/US2008/087846 n 195(3 ibb-UUU07 control expansion of the hydrogel, and as such, they are not incorporated into the apparatus and systems described herein.
[0027]
Further, the absence of metallic support members from the devices described herein allow for better resolution under various imaging procedures.
Metallic support members, for example, can distort the imaging of a device by producing flares or reflections from the metallic support members within the image.
As such, providing a device with no metallic support members, but including one or more visualization agents, such as radiopaque elements or fillers, as taught herein allows one skilled in the art to attain a more precise and accurate image of the device both during and after implantation. Such devices with no metallic support members may include support members not visible to imaging techniques, for example polymeric support members.
Further, the absence of metallic support members from the devices described herein allow for better resolution under various imaging procedures.
Metallic support members, for example, can distort the imaging of a device by producing flares or reflections from the metallic support members within the image.
As such, providing a device with no metallic support members, but including one or more visualization agents, such as radiopaque elements or fillers, as taught herein allows one skilled in the art to attain a more precise and accurate image of the device both during and after implantation. Such devices with no metallic support members may include support members not visible to imaging techniques, for example polymeric support members.
[0028] In another embodiment described herein is a method for preparing a device for implantation in an animal comprising the steps of combining a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; a visualization element, and a solvent to prepare a prepolymer solution; and treating the prepolymer solution to prepare hydrogel that is expansible at physiological conditions.
[0029] Generally, the prepolymer solution is comprised of a solvent, a difunctional, low molecular weight ethylenically unsaturated macromer, an ethylenically unsaturated monomer with one or more visualization agents, an ionizable ethylenically unsaturated monomer, one or more optional ethylenically unsaturated monomers with visualization agents either with or without radiopacity, and an optional porosigen. Alternatively, the prepolymer solution is comprised of a solvent, a difunctional ethylenically unsaturated macromer, optional ethylenically unsaturated monomer or monomers, optional cross-linkers, and one or more visualization agents, such as radiopaque elements or fillers, which include, but are not limited to, barium, tantalum, platinum, and gold.
[0030] The solvent in the prepolymer solution serves to completely dissolve of all macromers and monomers within the prepolymer solution. If a liquid monomer (e.g. 2-hydroxyethyl methacrylate) is used, a solvent may not be necessary.
The solvent, if necessary, is selected based on the solubility of the macromers and [PCT/US2008/087846 n 195(3 /88-UUU07 monomers. Preferred solvents are isopropyl alcohol (IPA, isopropanol), ethanol, water, dichloromethane, and acetone; however, a number of other solvents could be utilized and are know to those skilled in the art. Preferred solvent concentrations range from about 20% w/w to about 80% w/w of the prepolymer solution, more preferably about 40% w/w to about 60% w/w. In one preferred embodiment, the solvent concentration is about 33% w/w of the prepolymer solution.
The solvent, if necessary, is selected based on the solubility of the macromers and [PCT/US2008/087846 n 195(3 /88-UUU07 monomers. Preferred solvents are isopropyl alcohol (IPA, isopropanol), ethanol, water, dichloromethane, and acetone; however, a number of other solvents could be utilized and are know to those skilled in the art. Preferred solvent concentrations range from about 20% w/w to about 80% w/w of the prepolymer solution, more preferably about 40% w/w to about 60% w/w. In one preferred embodiment, the solvent concentration is about 33% w/w of the prepolymer solution.
[0031] The difunctional low molecular weight ethylenically unsaturated shapeable macromer serves to cross-link the polymer chains during polymerization and impart flexibility to the resulting polymer. Such macromers include at least one ethylenically unsaturated group and two functional sites. In one embodiment, at least one ethylenically unsaturated group can be one of the functional sites, or can be both functional sites. In one embodiment, the macromers described herein have a low molecular weight. The macromers described herein have a molecular weight ranging from about 100 g/mol to about 5,000 g/mole, or about 200 g/mole to about 2,500 g/mole, more preferably about 400 g/mole to about 1,000 g/mole. A
preferred macromer is poly(ethylene glycol) diacrylamide because of its biocompatibility and solubility in a wide variety of solvents. If degradation of the resulting polymer is desired, a preferred macromer is poly(ethylene glycol) diacrylate.
Alternatively, more hydrophobic macromers such as the polyethers poly(propylene glycol) and poly(tetramethylene oxide) or derivatives of polyolefins such as poly(ethylene) are suitable. Other suitable macromers include polyethylene glycol, propylene glycol, and poly(ethylene glycol) dimethacrylate.
preferred macromer is poly(ethylene glycol) diacrylamide because of its biocompatibility and solubility in a wide variety of solvents. If degradation of the resulting polymer is desired, a preferred macromer is poly(ethylene glycol) diacrylate.
Alternatively, more hydrophobic macromers such as the polyethers poly(propylene glycol) and poly(tetramethylene oxide) or derivatives of polyolefins such as poly(ethylene) are suitable. Other suitable macromers include polyethylene glycol, propylene glycol, and poly(ethylene glycol) dimethacrylate.
[0032] "Ethylenically unsaturated" as used herein generally describes a compound with a group such as, but not limited to, vinyl, acrylate, methacrylate, or acrylamide groups including derivatives thereof or combinations thereof.
[0033] A
"shapeable" macromer is used herein to describe the relative rigidity of the macromer and its ability to hold a particular shape. For example, a shapeable macromer according to the present description can be formed using a device such as a mandrel and can hold the resulting shape for implantation.
"shapeable" macromer is used herein to describe the relative rigidity of the macromer and its ability to hold a particular shape. For example, a shapeable macromer according to the present description can be formed using a device such as a mandrel and can hold the resulting shape for implantation.
[0034] The ethylenically unsaturated monomers with one or more visualization agents serve to impart visualization of the resulting polymer under the appropriate visualization method. In one embodiment, ethylenically unsaturated monomers [PCT/US2008/087846 n 195(3 /t3b-UUU07 comprise radiopaque elements or radiopaque elements alone which serve to impart radiopacity to the resulting polymer. Aromatic rings with single unsaturations and one or more iodine atom are preferred ethylenically unsaturated monomers with radiopaque elements. Examples include 2,4,6-triiodophenyl penta-4-enoate and 5-acrylamido-2,4,6-triiodo-n,n'-bis-(2,3 dihydroxypropyl) isophthalamide.
Preferred concentrations of the unsaturated monomer with radiopaque elements range from about 40% w/w to about 80% w/w of the prepolymer solution, more preferably about 40% w/w to about 60% w/w of the prepolymer solution. Alternatively, radiopaque elements or fillers such as tantalum, barium or salts thereof can be incorporated into the prepolymer solution either in place of the radiopaque elements or in addition to them. Radiopaque filler loadings range from about 40% w/w to about 60% w/w of the resulting polymer.
Preferred concentrations of the unsaturated monomer with radiopaque elements range from about 40% w/w to about 80% w/w of the prepolymer solution, more preferably about 40% w/w to about 60% w/w of the prepolymer solution. Alternatively, radiopaque elements or fillers such as tantalum, barium or salts thereof can be incorporated into the prepolymer solution either in place of the radiopaque elements or in addition to them. Radiopaque filler loadings range from about 40% w/w to about 60% w/w of the resulting polymer.
[0035]
"Visulaization agent" as used herein refers to any element that is added to or encompassed within the devices described herein that impart a means of visualizing the device either during or after implantation. Methods of visualization include, but are not limited to, x-rays, ultrasound, fluoroscopy, infrared radiation, ultraviolet light methods, magnetic resonance and combinations thereof. In one embodiment, the visualization agent can be one or more radiopaque elements or fillers which impart radiopacity to the devices described herein. In another embodiment, the visualization agent can be a non-radioapque element or filler such as gadolinium or iron oxide. Such non-radiopaque elements or fillers do not impart radiopacity to the devices described herein and can be imaged by, for example, magnetic resonance.
"Visulaization agent" as used herein refers to any element that is added to or encompassed within the devices described herein that impart a means of visualizing the device either during or after implantation. Methods of visualization include, but are not limited to, x-rays, ultrasound, fluoroscopy, infrared radiation, ultraviolet light methods, magnetic resonance and combinations thereof. In one embodiment, the visualization agent can be one or more radiopaque elements or fillers which impart radiopacity to the devices described herein. In another embodiment, the visualization agent can be a non-radioapque element or filler such as gadolinium or iron oxide. Such non-radiopaque elements or fillers do not impart radiopacity to the devices described herein and can be imaged by, for example, magnetic resonance.
[0036]
"Radiopaque" as used herein refers to elements or fillers as described above that impart radiopacity to the devices described herein and are detectable by a means of electrometric radiation such as, but not limited to, x-rays, ultrasound, fluoroscopy, infrared, ultraviolet and combinations thereof. In one embodiment, radiopaque elements described herein are detectable using x-rays or x-ray fluoroscopy.
"Radiopaque" as used herein refers to elements or fillers as described above that impart radiopacity to the devices described herein and are detectable by a means of electrometric radiation such as, but not limited to, x-rays, ultrasound, fluoroscopy, infrared, ultraviolet and combinations thereof. In one embodiment, radiopaque elements described herein are detectable using x-rays or x-ray fluoroscopy.
[0037] The ionizable ethylenically unsaturated monomer serves to delay the expansion of the hydrogel filament, thereby establishing a controlled rate of expansion. In one embodiment, at least a portion, preferably about 5% to about 50%
w/w of the monomer solution, more preferably about 5% to about 25% w/w of the [PCT/US2008/087846 n 195(3 ibb-UUU07 prepolymer solution, of the monomers selected are ionizable. The preferred ionizable monomers may be acrylic acid or methacrylic acid. Derivatives and salts of both acids are also suitable ionizable components. Alternatively, in one embodiment, ionizable ethylenically unsaturated monomers are not utilized.
w/w of the monomer solution, more preferably about 5% to about 25% w/w of the [PCT/US2008/087846 n 195(3 ibb-UUU07 prepolymer solution, of the monomers selected are ionizable. The preferred ionizable monomers may be acrylic acid or methacrylic acid. Derivatives and salts of both acids are also suitable ionizable components. Alternatively, in one embodiment, ionizable ethylenically unsaturated monomers are not utilized.
[0038] In one embodiment optional ethylenically unsaturated monomers with a visualization agent that does or does not impart radiopacity to the devices are used to aid the polymerization process and can be any mono or multifunctional ethylenically unsaturated compound. In one embodiment, ethylenically unsaturated monomers with visualization agents without radiopacity with low molecular weights are preferred. Hydroxyethyl methacrylate (e.g. 2-hydroxyetyl methacrylate), hydroxyethyl acrylate, N-vinyl pyrrolidinone and N, N'-methylenebisacrylamide are preferred ethylenically unsaturated monomers visualization agents without radiopacity. Preferred concentrations of the ethylenically unsaturated monomers visualization agents without radiopacity are less than about 5% w/w, more preferably less than about 1% w/w of the prepolymer solution.
[0039] In one embodiment, the hydrogels and devices described herein further comprise visualization agents, such as, gadolinium or iron oxide in addition to radiopaque elements to impart visibility of the devices under magnetic resonance imaging. In other embodiments, the gadolinium or iron oxide are used instead of or in place of the radiopaque elements.
[0040] The optional porosigen serves to impart pores in the resulting polymer.
The porosity of the hydrogel material is imparted as a result of a supersaturated suspension of a porosigen in the prepolymer solution. A porosigen that is not soluble in the prepolymer solution, but is soluble in the washing solution, can also be used. In one embodiment, sodium chloride is the preferred porosigen. In other embodiments, ice, sucrose, and sodium bicarbonate can also be used as porosigens. It is preferred that the particle size of the porosigen be less than about 25 microns, more preferably less than about 10 microns. The small particle sizes aid the suspension of the porosigen in the solvent. Preferred concentrations of the porosigen are less than about 50% w/w, more preferably less than about 20% w/w of the prepolymer solution. In some embodiments according to the present description a porosigen is not utilized.
[PCT/US2008/087846 n 195(3 ibb-UUU07
The porosity of the hydrogel material is imparted as a result of a supersaturated suspension of a porosigen in the prepolymer solution. A porosigen that is not soluble in the prepolymer solution, but is soluble in the washing solution, can also be used. In one embodiment, sodium chloride is the preferred porosigen. In other embodiments, ice, sucrose, and sodium bicarbonate can also be used as porosigens. It is preferred that the particle size of the porosigen be less than about 25 microns, more preferably less than about 10 microns. The small particle sizes aid the suspension of the porosigen in the solvent. Preferred concentrations of the porosigen are less than about 50% w/w, more preferably less than about 20% w/w of the prepolymer solution. In some embodiments according to the present description a porosigen is not utilized.
[PCT/US2008/087846 n 195(3 ibb-UUU07
[0041] The prepolymer solution can be cross-linked by reduction-oxidation, radiation, heat, or any other method known in the art. Radiation cross-linking of the prepolymer solution can be achieved with ultraviolet light or visible light with suitable initiators or ionizing radiation (e.g. electron beam or gamma ray) without initiators.
Cross-linking can be achieved by application of heat, either by conventionally heating the solution using a heat source such as a heating well, or by application of infrared light to the prepolymer solution.
Cross-linking can be achieved by application of heat, either by conventionally heating the solution using a heat source such as a heating well, or by application of infrared light to the prepolymer solution.
[0042] In a preferred embodiment, the cross-linking method utilizes azobisisobutyronitrile (AIBN) or another water soluble AIBN derivative (2,2'-azobis(2-methylpropionamidine) dihydrochloride). Other cross-linking agents useful according to the present description include N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxides, and combinations thereof, including azobisisobutyronitriles. In one embodiment, the AIBN or derivative thereof is used at an elevated temperature. After addition of AIBN, the prepolymer solution is injected into poly(ethylene) tubing with an inner diameter ranging from 0.012 inches to 0.075 inches and incubated for several hours at 80 C. The selection of the poly(ethylene) tubing imparts microcatheter or catheter compatibility. For delivery through microcatheters, poly(ethylene) tubing diameters from about 0.012 inches to about 0.025 inches are preferred. For delivery through 5 French Size (Fr) catheters, poly(ethylene) tubing diameters from about 0.030 inches to about 0.050 inches are preferred. Alternatively, HYTREL (DuPont, Wilmington, DE) tubing of the same diameter can be utilized. The HYTREL tubing can be dissolved in solvents, facilitating removal of the polymer from the tubing.
[0043] If the poly(ethylene) tubing is wrapped around a mandrel prior to polymerization of the prepolymer solution, the resulting polymer will maintain the shape of the poly(ethylene) or HYTREL tubing, primarily as a result of the shapeable macromer within the prepolymer solution. Using this technique, helical, tornado, and complex shapes can be imparted to the polymer. The memory of the imparted shape is strongly influenced by the macromer selection. More hydrophobic macromers retain their imparted shape better than more hydrophilic macromers.
It is preferred that an ethylenically unsaturated shapeable macromer be used in this embodiment.
[PCT/US2008/087846 n 195(3 ibb-UUU07
It is preferred that an ethylenically unsaturated shapeable macromer be used in this embodiment.
[PCT/US2008/087846 n 195(3 ibb-UUU07
[0044] In one embodiment, the devices described herein are environmentally responsive. Environmentally responsive as used herein means that the devices change in some way in response to the surrounding environment. In one embodiment, this response to the surrounding environment is in the form of a controlled rate of expansion. A controlled rate of expansion of the hydrogels described herein is achieved through the protonation/deprotonation of ionizable functional groups present within or on the hydrogel network. Once the hydrogel has been prepared and the unincorporated macromers, monomers, and oligomers have been washed away, the steps to control the rate of expansion can be performed.
[0045] If monomers with carboxylic acid groups are incorporated into the hydrogel network, the hydrogel is incubated in a low pH solution. The free protons in the solution protonate the carboxylic acid groups within the hydrogel network. The length of incubation, temperature during incubation, and pH of the solution influence the amount of control on the expansion rate. Generally, the length and temperature of the incubation are directly proportional to the amount of expansion control, while solution pH is inversely proportional. Surprisingly, it was found that the water content of the treating solution also affects the expansion control. As the water content increases, the hydrogel is able to expand more in the treating solution and it is presumed that an increased number of carboxylic acid groups are available for protonation. An optimization of water content and pH can be required for maximum control of the expansion rate. After the incubation is concluded, the excess treating solution is washed away and the hydrogel material is dried. It has been observed that hydrogel treated with the low pH solution dries down to a smaller dimension than the untreated hydrogel. In one embodiment, smaller dimensioned hydrogels are utilized since delivery of these hydrogel materials through a microcatheter is desired.
[0046] In contrast, if pH sensitive monomers with amine groups are incorporated into or on the hydrogel network, the hydrogel is incubated in a high pH
solution.
Deprotonation occurs on the amine groups of the hydrogel network at high pH.
The length of incubation, temperature during incubation, and pH of the solution influence the amount of control on the expansion rate. Generally, the length and temperature of the incubation and solution pH are directly proportional to the amount of expansion control. After the incubation is concluded, the excess treating solution is washed away and the hydrogel material is dried.
[PCT/US2008/087846 n 195(3 ibb-UUU07
solution.
Deprotonation occurs on the amine groups of the hydrogel network at high pH.
The length of incubation, temperature during incubation, and pH of the solution influence the amount of control on the expansion rate. Generally, the length and temperature of the incubation and solution pH are directly proportional to the amount of expansion control. After the incubation is concluded, the excess treating solution is washed away and the hydrogel material is dried.
[PCT/US2008/087846 n 195(3 ibb-UUU07
[0047] In some embodiments according to the present description, non-aqueous solvents are utilized. In such embodiments, monomers with protonated carboxylic acids (e.g., acrylic acid or methacrylic acid) can be used in place of their corresponding salts (e.g. sodium acrylate or sodium methacrylate). The use of these monomers in non-aqueous solvents obviates the need for subsequent treatment in low pH solutions.
[0048]
After the cross-linked hydrogel has been washed, it is dried and a dried hydrogel filament is produced. The length can range from about 0.5 cm to about cm and the diameter can range from about 0.010 inches to about 0.100 inches.
In some embodiments, a pushable embolic device is required. In these instances, the dried hydrogel filament is loaded into introducer tubing, packaged, and sterilized.
Upon receipt, the surgeon pushes the dried hydrogel filament into the microcatheter or catheter with a wire or other pusher. The dried hydrogel filament is then advanced down the microcatheter or catheter to the embolization site.
After the cross-linked hydrogel has been washed, it is dried and a dried hydrogel filament is produced. The length can range from about 0.5 cm to about cm and the diameter can range from about 0.010 inches to about 0.100 inches.
In some embodiments, a pushable embolic device is required. In these instances, the dried hydrogel filament is loaded into introducer tubing, packaged, and sterilized.
Upon receipt, the surgeon pushes the dried hydrogel filament into the microcatheter or catheter with a wire or other pusher. The dried hydrogel filament is then advanced down the microcatheter or catheter to the embolization site.
[0049] In one embodiment, the hydrogels described herein are substantially free of acrylamide. Consequently, the hydrogels substantially free of acrylamide have less than about 1% (w/w%) acrylamide per hydrogel mass. In other embodiments, the acrylamide is less than about 0.5% or less than about 0.01 (:)/0 of the hydrogel mass.
[0050] In other embodiments, the hydrogel is non-bioresorbable or substantially non-bioresorbable. A "non-bioresorbable" hydrogel as used herein is biocompatible and not subject to breakdown in vivo through the action of normal biochemical pathways. In one embodiment, the hydrogel is substantially non-bioresorbable and remains greater than 95% intact after 1 year of implantation. In other embodiments, the substantially non-bioresorbable hydrogel remains greater than 90% intact after 1 year.
[0051] In yet a further embodiment, the hydrogel is bioresorbable, meaning the hydrogel is biocompatible and is broken down in vivo through the action of normal biochemical pathways. In one embodiment, the hydrogel is bioresorbable and remains less than 5% intact after 1 year of implantation. In other embodiments, the hydrogel is bioresorbable and remains less than 5% intact after 2 years of [PCT/US2008/087846 n 195(3 ibb-UUU07 implantation. In other embodiments, the hydrogel is bioresorbable and remains less than 5% intact after 5 years of implantation.
[0052] In another embodiment according to the present description, a retrievable embolic device is required. In these instances, a coupler is attached to a dried hydrogel filament by gluing, swaging, or other means known in the art. The coupler permits attachment to a delivery pusher. After attachment to the delivery pusher, the dried hydrogel filament/delivery pusher construct is packaged and sterilized.
Upon receipt, a surgeon introduces the device into a microcatheter or catheter and advances it to the embolization site. The surgeon can retract and advance the device until it is positioned adequately. At this time, the surgeon can detach the dried hydrogel filament from the delivery pusher and remove the delivery pusher from the microcatheter or catheter.
Upon receipt, a surgeon introduces the device into a microcatheter or catheter and advances it to the embolization site. The surgeon can retract and advance the device until it is positioned adequately. At this time, the surgeon can detach the dried hydrogel filament from the delivery pusher and remove the delivery pusher from the microcatheter or catheter.
[0053] In another embodiment, a fluid assisted injectable embolic device is used.
In this case, a dried hydrogel filament is loaded into an introducer, packaged, and sterilized. Upon receipt, the surgeon injects the dried hydrogel filament into the microcatheter or catheter with a syringe filled with saline or other physiological solution. The saline or other physiological solution is used to assist in advancing the hydrogel filament down the catheter in addition to hydrating it. The dried hydrogel filament is then advanced down the microcatheter or catheter to the embolization site with subsequent injections.
Examples
In this case, a dried hydrogel filament is loaded into an introducer, packaged, and sterilized. Upon receipt, the surgeon injects the dried hydrogel filament into the microcatheter or catheter with a syringe filled with saline or other physiological solution. The saline or other physiological solution is used to assist in advancing the hydrogel filament down the catheter in addition to hydrating it. The dried hydrogel filament is then advanced down the microcatheter or catheter to the embolization site with subsequent injections.
Examples
[0054] The following are non-limiting examples of some of the biomedical applications of hydrogels with visualization agents described herein. It will be appreciated, however, that this material has many other medical and non-medical applications in addition to the specific examples set forth herein.
Example 1 Preparation of PEG 1000 Diacrvlamide
Example 1 Preparation of PEG 1000 Diacrvlamide
[0055]
First, 18 g of polyethylene glycol (PEG) 1000 was dried by azeotropic distillation with 200 mL of toluene. Then, 7.0 mL of triethylamine was added with 4.6 mL of mesyl chloride and stirred for 4 hr. The solution was then filtered to remove salt and the solvent evaporated. The resulting product was added to 150 mL of 25%
[PCT/US2008/087846 n 195(3 ibb-UUU07 ammonia hydroxide and stirred for 2 days. The water was removed and the product dried by azeotropic distillation with toluene. The resulting dried PEG diamine was dissolved in 20 mL dichloromethane and 50 mL toluene. Then, 7.0 mL of triethylamine and 4.9 mL of acryloyl chloride were added and the reaction proceeded for 4 hr while stirring. The resulting solution was filtered and the solvent was removed leaving PEG 1000 diacrylamide.
Example 2 Preparation of a Radiopaque Monomer
First, 18 g of polyethylene glycol (PEG) 1000 was dried by azeotropic distillation with 200 mL of toluene. Then, 7.0 mL of triethylamine was added with 4.6 mL of mesyl chloride and stirred for 4 hr. The solution was then filtered to remove salt and the solvent evaporated. The resulting product was added to 150 mL of 25%
[PCT/US2008/087846 n 195(3 ibb-UUU07 ammonia hydroxide and stirred for 2 days. The water was removed and the product dried by azeotropic distillation with toluene. The resulting dried PEG diamine was dissolved in 20 mL dichloromethane and 50 mL toluene. Then, 7.0 mL of triethylamine and 4.9 mL of acryloyl chloride were added and the reaction proceeded for 4 hr while stirring. The resulting solution was filtered and the solvent was removed leaving PEG 1000 diacrylamide.
Example 2 Preparation of a Radiopaque Monomer
[0056]
First, 9 g of triiodophenol was dissolved in 150 mL dichloromethane under argon. Then, 3.15 mL of pentenoyl chloride was added while stirring.
Triethylamine was then added slowly and stirred for 4 hr. The solution was washed with 100 mL of water and evaporated to dryness, leaving 2,4,6-triiodophenyl penta-4-enoate.
Example 3 Preparation of a Radiopaque 1-lvdroqe1 Filament in Chloroform
First, 9 g of triiodophenol was dissolved in 150 mL dichloromethane under argon. Then, 3.15 mL of pentenoyl chloride was added while stirring.
Triethylamine was then added slowly and stirred for 4 hr. The solution was washed with 100 mL of water and evaporated to dryness, leaving 2,4,6-triiodophenyl penta-4-enoate.
Example 3 Preparation of a Radiopaque 1-lvdroqe1 Filament in Chloroform
[0057] To prepare a radiopaque hydrogel in an organic solvent, 2 g of 2,4,6-triiodophenyl penta-4-enoate, 0.67 g of acrylic acid, 1.2 g of PEG
diacrylamide 400, 24 mg of N,N-methylenebisacrylamide and 75 mg of azobis(2-methylpropionitrile) were dissolved in 2.5 mL of chloroform. Then, the solution was sparged with argon for 10 min before injection into a 0.020 inch polyethylene tubing using a 3cc syringe.
The tubes were heat sealed at both ends and placed in an 80 C oven overnight to polymerize the solution.
Example 4 Preparation of a Barium Loaded Radiopaque 1-lvdroqe1 Filament
diacrylamide 400, 24 mg of N,N-methylenebisacrylamide and 75 mg of azobis(2-methylpropionitrile) were dissolved in 2.5 mL of chloroform. Then, the solution was sparged with argon for 10 min before injection into a 0.020 inch polyethylene tubing using a 3cc syringe.
The tubes were heat sealed at both ends and placed in an 80 C oven overnight to polymerize the solution.
Example 4 Preparation of a Barium Loaded Radiopaque 1-lvdroqe1 Filament
[0058] To prepare a barium-loaded radiopaque hydrogel in an organic solvent, 7 g of barium sulfate, 0.5 g of acrylic acid, 5 g of poly(tetramethylene oxide) diacrylamide 1000, 1.25 g of 2-hydroxyethylemethacrylate, 212 mg of N,N-methylenebisacrylamide and 100 mg of azobis(2-methylpropionitrile) were dissolved in 3.5 mL of isopropyl alcohol. The solution was then sparged with argon for 10 min before injection into 0.010 inch HYTREL tubing wrapped around a 4 mm mandrel using a 3cc syringe. The tubes were heat sealed at both ends and placed in a 100 C water bath for 1 hr, then overnight in an 80 C oven to polymerize the solution.
[PCT/US2008/087846 on 195(3 ibb-UUU07 Example 5 Preparation of a Radiopaque livdrogel Filament in Water
[PCT/US2008/087846 on 195(3 ibb-UUU07 Example 5 Preparation of a Radiopaque livdrogel Filament in Water
[0059] To prepare a radiopaque hydrogel in water, 5 g of 2,5-acrylamido-2,4,6-triiodo-n,n'-bis-(2,3 dihydroxypropyl) isophthalamide, 1.33 g of acrylic acid, 2.5 g PEG diacrylamide 400, 50 mg of n-vinyl-2-pyrrolidinone and 100 mg of 2,2'azobis(2-methylpropionamidine) dihydrochloride were dissolved in 10 mL of water. The solution was then sparged with argon for 10 min before injection into 0.020 inch polyethylene tubing using a 3cc syringe. The tubes were heat sealed at both ends and placed in an 80 C oven overnight to polymerize the solution.
Example 6 Washing and Acid Treatment of a Radiopaque livdrogel Filament
Example 6 Washing and Acid Treatment of a Radiopaque livdrogel Filament
[0060] For the hydrogel polymerized according to Example 3, the tubes were cut into 3 inch sections and placed in acetone for 1 hr. In acetone, the hydrogel expanded out the ends of the tubes, allowing it to be removed from the tube.
The hydrogel was washed in acetone for 2 hr. After 2 hr, the acetone was exchanged and the hydrogel was washed for another 2 hr. The acetone was removed and the hydrogel dried in a vacuum oven for 2 hr at 50 C.
The hydrogel was washed in acetone for 2 hr. After 2 hr, the acetone was exchanged and the hydrogel was washed for another 2 hr. The acetone was removed and the hydrogel dried in a vacuum oven for 2 hr at 50 C.
[0061] For hydrogels polymerized according to Example 4, the hydrogel was removed by dissolving the tubing in a solution of 20% phenol in chloroform.
After the tubing was dissolved, the phenol solution was exchanged with chloroform and washed for 1 hr. After 1 hr, the chloroform was exchanged and the hydrogel washed for another 1 hr. The chloroform was removed and the hydrogel dried in a vacuum oven for 2 hr at 50 C. To remove any unreacted monomers, the hydrogel was placed in ethanol for 12 hr. After 12 hr, the ethanol was exchanged and washed for 2 hr. After 2 hr, the ethanol was exchanged and the hydrogel washed for another 2 hr. The ethanol was removed and hydrogel dried in a vacuum oven for 12 hr.
After the tubing was dissolved, the phenol solution was exchanged with chloroform and washed for 1 hr. After 1 hr, the chloroform was exchanged and the hydrogel washed for another 1 hr. The chloroform was removed and the hydrogel dried in a vacuum oven for 2 hr at 50 C. To remove any unreacted monomers, the hydrogel was placed in ethanol for 12 hr. After 12 hr, the ethanol was exchanged and washed for 2 hr. After 2 hr, the ethanol was exchanged and the hydrogel washed for another 2 hr. The ethanol was removed and hydrogel dried in a vacuum oven for 12 hr.
[0062] For the hydrogel polymerized according to Example 5, the tubes were cut into 3 inch sections and placed in the vacuum oven for 6 hr at 50 C. Once the hydrogel was dried, it can be pushed out of the tubes using a mandrel. The hydrogel was washed in water for 2 hr. After 2 hr the water was exchanged and the hydrogel [PCT/US2008/087846 n 195(3 ibb-UUU07 was washed for another 2 hr. The water was removed and the hydrogel dried in a vacuum oven for 2 hr at 50 C.
[0063]
Acid treatment of the hydrogels consisted of incubating in 1N hydrochloric acid (FICI) for 4 hr at 37 C. After 4 hr the acid was decanted off. The hydrogel was incubated in 99% isopropyl alcohol for 1 hr to remove any remaining acid. The hydrogel was dried in a vacuum oven for 1 hr at 50 C to remove the remaining isopropyl alcohol.
Example 7 Attachment of a Radiopaque livdrogel Filament to a Pusher
Acid treatment of the hydrogels consisted of incubating in 1N hydrochloric acid (FICI) for 4 hr at 37 C. After 4 hr the acid was decanted off. The hydrogel was incubated in 99% isopropyl alcohol for 1 hr to remove any remaining acid. The hydrogel was dried in a vacuum oven for 1 hr at 50 C to remove the remaining isopropyl alcohol.
Example 7 Attachment of a Radiopaque livdrogel Filament to a Pusher
[0064] The radiopaque hydrogel filament can be attached to a V-TRAKO
(MicroVention Terumo, Inc., Aliso Viejo, CA) or hydraulic pusher. To attach the hydrogel to a V-TRAKO pusher, a section of 0.0022 inch poly(ethylene) tubing suture was threaded through a coupler. The coupler consisted of a titanium cylinder hollowed out on one end and a through hole. The poly(ethylene) tubing suture was tied into a knot such that it could not be pulled back through. The hydrogel was glued into the coupler on top of the knot using adhesive. The other end of the poly(ethylene) tubing thread was threaded into a V-TRAKO pusher and tied.
(MicroVention Terumo, Inc., Aliso Viejo, CA) or hydraulic pusher. To attach the hydrogel to a V-TRAKO pusher, a section of 0.0022 inch poly(ethylene) tubing suture was threaded through a coupler. The coupler consisted of a titanium cylinder hollowed out on one end and a through hole. The poly(ethylene) tubing suture was tied into a knot such that it could not be pulled back through. The hydrogel was glued into the coupler on top of the knot using adhesive. The other end of the poly(ethylene) tubing thread was threaded into a V-TRAKO pusher and tied.
[0065] To attach the hydrogel to a hydraulic pusher, a bullet coupler was used.
The gel was glued into the coupler using adhesive and attached to a hydraulic pusher using heat shrink PET tubing.
Example 8 Measurement of Buckling Force
The gel was glued into the coupler using adhesive and attached to a hydraulic pusher using heat shrink PET tubing.
Example 8 Measurement of Buckling Force
[0066] To compare the ability of the radiopaque hydrogel filament of Example 6 to deploy inside aneurysm sacs with other currently marketed coils, the buckling force of a variety of devices was determined. In this test, approximately one inch pieces of the devices were attached to about 15 inch pieces of hypo tubing by either soldering or poly(ethylene) shrink tubing. The hypo tubing end of the constructs was attached to an Instron 5543 Single Column Testing System, a system used to measure force data of materials. The construct was advanced down a dead end channel in a poly(carbonate) block. When the device reached the bottom of the channel, it was forced to buckle and the corresponding force was measured.
[PCT/US2008/087846 on 195(3 ibb-UUU07 Group Buckling Force (gf) HYPERSOFTO Platinum Coil 0.6 0.4 (MicroVention Terumo, Inc., Aliso Viejo, CA) MICROPLEXO Platinum Coil 0.010 2.3 1.0 inch (MicroVention Terumo, Inc., Aliso Viejo, CA) (MicroVention Terumo, Inc., Aliso Viejo, CA) Radiopaque Hydrogel Filament 0.5 0.4
[PCT/US2008/087846 on 195(3 ibb-UUU07 Group Buckling Force (gf) HYPERSOFTO Platinum Coil 0.6 0.4 (MicroVention Terumo, Inc., Aliso Viejo, CA) MICROPLEXO Platinum Coil 0.010 2.3 1.0 inch (MicroVention Terumo, Inc., Aliso Viejo, CA) (MicroVention Terumo, Inc., Aliso Viejo, CA) Radiopaque Hydrogel Filament 0.5 0.4
[0067]
Three types of currently marketed coil systems were tested and compared to the radiopaque hydrogel filament of Example 6. The first coil tested was a HYPERSOFTO Platinum Coil. The HYPERSOFTO Platinum coil is a soft platinum finishing coil with an outer diameter of 0.012 inch and a filar size of 0.002 inch. The second coil tested was a MICROPLEXO Platinum Coil. The MICROPLEXO Platinum coil is a platinum filling coil with an outer diameter of 0.010 inch and a filar size of 0.002 inch. The HYPERSOFTO Platiumun coil and MICROPLEXO Platinum coil are soft platinum helical coils with no expandable hydrogel. The third coil tested was a HYDROCOILO 10 system. The HYDROCOILO 10 system is a platinum coil with an outer diameter of 0.008 inch and a filar size of 0.002 inch jacketed with an expandable poly (acrylamide-co-acrylic acid) hydrogel and overcoiled with a stretched platinum coil.
Three types of currently marketed coil systems were tested and compared to the radiopaque hydrogel filament of Example 6. The first coil tested was a HYPERSOFTO Platinum Coil. The HYPERSOFTO Platinum coil is a soft platinum finishing coil with an outer diameter of 0.012 inch and a filar size of 0.002 inch. The second coil tested was a MICROPLEXO Platinum Coil. The MICROPLEXO Platinum coil is a platinum filling coil with an outer diameter of 0.010 inch and a filar size of 0.002 inch. The HYPERSOFTO Platiumun coil and MICROPLEXO Platinum coil are soft platinum helical coils with no expandable hydrogel. The third coil tested was a HYDROCOILO 10 system. The HYDROCOILO 10 system is a platinum coil with an outer diameter of 0.008 inch and a filar size of 0.002 inch jacketed with an expandable poly (acrylamide-co-acrylic acid) hydrogel and overcoiled with a stretched platinum coil.
[0068]
Statistically significant differences in the buckling force of the radiopaque hydrogel filament and the HYPERSOFTO Platiumun coil, an extremely soft platinum coil, were not observed. This experiment demonstrated that the radiopaque hydrogel filament has soft deployment characteristics suitable for embolic devices.
Example 9 Measurement of Bending Resistance
Statistically significant differences in the buckling force of the radiopaque hydrogel filament and the HYPERSOFTO Platiumun coil, an extremely soft platinum coil, were not observed. This experiment demonstrated that the radiopaque hydrogel filament has soft deployment characteristics suitable for embolic devices.
Example 9 Measurement of Bending Resistance
[0069] The bending resistance of the unexpanded hydrogel samples and the bending resistance of injectable platinum microcoils were obtained using a Gurley 4171ET tubular sample stiffness tester with a 5 g counterweight attached to its [PCT/US2008/087846 n 195(3 ibb-UUU07 measuring vane. The sample length was one inch. The average of three replicates each are summarized in the following table.
Sample Measured Resistance (mg) D-51 radiopaque 0.9 0.4 hydrogel filament 0.008 inch platinum 0.6 0.2 microcoil
Sample Measured Resistance (mg) D-51 radiopaque 0.9 0.4 hydrogel filament 0.008 inch platinum 0.6 0.2 microcoil
[0070] The results illustrate little difference in relative stiffness between the radiopaque hydrogel filament and the platinum microcoil. The results demonstrate that the flexibility of an injectable platinum coil can be achieved with a radiopaque hydrogel filament.
Example 10 Evaluation of an Injectable Radiopaque Flvdrogel Filament
Example 10 Evaluation of an Injectable Radiopaque Flvdrogel Filament
[0071]
Devices constructed from barium loaded radiopaque hydrogel formulations were evaluated in a flow model fitted with a torturous vessel. A flow directed microcatheter (Boston Scientific Spinnaker 1.5 F) was placed in the vessel.
Devices ranging from 5 cm to 30 cm in length were injected through the microcatheter using a 3cc syringe. The devices were evaluated on introduction, tracking, deployment and packing. To achieve a pass for Intro, Tracking, and Deploy, the implant must introduce, track and deploy using a 3cc syringe without incident. To achieve a pass for packing, the implant must pack in a torturous vessel similar to a 0.008 inch platinum coil.
Formulation Intro Tracking Deploy Packing D-51 radiopaque Pass Pass Pass Pass hydrogel filament 0.008 inch platinum Pass Pass Pass Pass coil
Devices constructed from barium loaded radiopaque hydrogel formulations were evaluated in a flow model fitted with a torturous vessel. A flow directed microcatheter (Boston Scientific Spinnaker 1.5 F) was placed in the vessel.
Devices ranging from 5 cm to 30 cm in length were injected through the microcatheter using a 3cc syringe. The devices were evaluated on introduction, tracking, deployment and packing. To achieve a pass for Intro, Tracking, and Deploy, the implant must introduce, track and deploy using a 3cc syringe without incident. To achieve a pass for packing, the implant must pack in a torturous vessel similar to a 0.008 inch platinum coil.
Formulation Intro Tracking Deploy Packing D-51 radiopaque Pass Pass Pass Pass hydrogel filament 0.008 inch platinum Pass Pass Pass Pass coil
[0072] The results illustrate that the radiopaque hydrogel filaments can be deployed into a simulated use torturous path and perform consistent with other embolic devices such as platinum coils.
[PCT/US2008/087846 n 195(3 /t3b-UUU07 Example 11 Evaluation of Radiopaque Polymer Hydrogel in Experimental Aneurysms
[PCT/US2008/087846 n 195(3 /t3b-UUU07 Example 11 Evaluation of Radiopaque Polymer Hydrogel in Experimental Aneurysms
[0073]
Three rabbit elastase aneurysms were embolized with radiopaque polymer filaments. The aneurysm width, length, and neck ranged from 2.4 to 3.6 mm, 4.7 to 8.8 mm, and 2.4 to 4.2 mm, respectively. A microcatheter (Gordis RAPIDTRANSITO, Gordis Corporation, Miami Lake, FL) was placed inside the aneurysm sac. One to three radiopaque hydrogel filaments were deployed inside the aneurysm sac. Angiography demonstrated complete occlusion of all three aneurysms as a result of the embolization. At 6 wk post-embolization, complete occlusion of all three aneurysms was demonstrated by angiography. The aneurysms were harvested and histologically processed. The sections demonstrated complete filling of the aneurysm sac with the radiopaque hydrogel filaments, organizing/organized fibrous tissue in the clefts between the radiopaque hydrogel filaments, and an inflammatory response consisting of macrophages and a few giant cells. These results illustrated that the radiopaque hydrogel filaments can be deployed into experimental aneurysms and elicit a foreign body response consistent with other embolic devices.
Three rabbit elastase aneurysms were embolized with radiopaque polymer filaments. The aneurysm width, length, and neck ranged from 2.4 to 3.6 mm, 4.7 to 8.8 mm, and 2.4 to 4.2 mm, respectively. A microcatheter (Gordis RAPIDTRANSITO, Gordis Corporation, Miami Lake, FL) was placed inside the aneurysm sac. One to three radiopaque hydrogel filaments were deployed inside the aneurysm sac. Angiography demonstrated complete occlusion of all three aneurysms as a result of the embolization. At 6 wk post-embolization, complete occlusion of all three aneurysms was demonstrated by angiography. The aneurysms were harvested and histologically processed. The sections demonstrated complete filling of the aneurysm sac with the radiopaque hydrogel filaments, organizing/organized fibrous tissue in the clefts between the radiopaque hydrogel filaments, and an inflammatory response consisting of macrophages and a few giant cells. These results illustrated that the radiopaque hydrogel filaments can be deployed into experimental aneurysms and elicit a foreign body response consistent with other embolic devices.
[0074] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[PCT/US2008/087846 n 195(3 ibb-UUU07
Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[PCT/US2008/087846 n 195(3 ibb-UUU07
[0075] The terms "a," "an," "the" and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0076]
Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
[0077]
Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein.
Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.
Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
=
Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein.
Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.
Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
=
[0078]
[0079] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention.
Other modifications that may be employed are within the scope of the invention.
Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein.
Accordingly, the present invention is not limited to that precisely as shown and described.
Other modifications that may be employed are within the scope of the invention.
Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein.
Accordingly, the present invention is not limited to that precisely as shown and described.
[0080] Specific embodiments disclosed herein may be further limited in the claims using consisting of or and consisting essentially of language. When used in the claims, whether as filed or added per amendment, the transition term "consisting of' excludes any element, step, or ingredient not specified in the claims. The transition term "consisting essentially of' limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s).
Embodiments of the invention so claimed are inherently or expressly described and enabled herein.
Embodiments of the invention so claimed are inherently or expressly described and enabled herein.
Claims (17)
1. A device for implantation comprising:
a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer;
an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 ~ 0.4 gf.
a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer;
an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 ~ 0.4 gf.
2. The device according to claim 1 wherein said macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.
3. The device according to claim 1 wherein said hydrogel filament is environmentally-responsive.
4. The device according to claim 1 wherein said macromer comprises polyethylene glycol, propylene glycol, poly(tetramethylene oxide), poly(ethylene glycol)diacrylamide, poly(ethylene glycol)diacrylate, poly(ethylene glycol)dimethacrylate, derivatives thereof, or combinations thereof.
5. The device according to claim 1 wherein said ethylenically unsaturated monomer comprises one or more ionizable functional groups.
6. The device according to claim 1 wherein said ethylenically unsaturated monomer comprises N,N'-methylenebisacrylamide, N-vinyl pyrrolidinone, 2-hydroxyethyl methacrylate, derivatives thereof, or combinations thereof.
7. The device according to claim 1 wherein said visualization agent comprises an aromatic ring having a single unsaturation point and at least one iodine atom.
8. The device according to claim 1 wherein said visualization agent comprises gadolinium or iron oxide.
9. The device according to claim I wherein said ethylenically unsaturated monomer and said visualization element comprise 2,4,6-triiodophenyl penta-4-enoate, 5-acrylamido-2,4,6-triiodo-n,n'-bis-(2,3 dihydroxypropyl) isophthalamide, derivatives thereof, or combinations thereof.
10. The device according to claim 1 wherein said macromer and said monomer are crosslinked with N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2'-azobis(2-methylpropionamidine)dihydrochloride, derivatives thereof, or combinations thereof.
11. The device according to claim 1 wherein said ethylenically unsaturated monomer includes one or more ionizable functional groups comprising basic groups or acidic groups.
12. The device according to claim 11 wherein said ionizable functional groups comprise amine groups, derivatives thereof, or combinations thereof
13. The device according to claim 11 wherein said acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.
14. The device according to claim 1 wherein said hydrogel filament is substantially free of acrylamide.
15. The device according to claim 1 wherein said hydrogel filament is substantially non-bioresorbable.
16. The device according to claim 1 wherein said hydrogel filament is bioresorbable.
17. A device for implantation in an animal comprising:
a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole;
an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 ~ 0.4 gf.
a hydrogel filament comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole;
an ethylenically unsaturated monomer; and a visualization agent, wherein said device contains no support members and wherein the hydrogel filament has a buckling force of 0.5 ~ 0.4 gf.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1634207P | 2007-12-21 | 2007-12-21 | |
US61/016,342 | 2007-12-21 | ||
PCT/US2008/087846 WO2009086208A2 (en) | 2007-12-21 | 2008-12-19 | Hydrogel filaments for biomedical uses |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2709379A1 CA2709379A1 (en) | 2009-07-09 |
CA2709379C true CA2709379C (en) | 2016-08-16 |
Family
ID=40287923
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2709379A Active CA2709379C (en) | 2007-12-21 | 2008-12-19 | Hydrogel filaments for biomedical uses |
Country Status (9)
Country | Link |
---|---|
US (3) | US8470035B2 (en) |
EP (2) | EP2266639B1 (en) |
JP (1) | JP5698537B2 (en) |
KR (1) | KR101567111B1 (en) |
CN (1) | CN101903051B (en) |
AU (1) | AU2008345590B2 (en) |
BR (1) | BRPI0821070B1 (en) |
CA (1) | CA2709379C (en) |
WO (1) | WO2009086208A2 (en) |
Families Citing this family (191)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007047851A2 (en) | 2005-10-19 | 2007-04-26 | Pulsar Vascular, Inc. | Methods and systems for endovascularly clipping and repairing lumen and tissue defects |
CA2649905C (en) | 2006-04-20 | 2019-04-09 | Dentatek Corporation | Apparatus and methods for treating root canals of teeth |
JP2010500917A (en) | 2006-06-15 | 2010-01-14 | マイクロベンション, インコーポレイテッド | Embolization device composed of expandable polymer |
US7980854B2 (en) | 2006-08-24 | 2011-07-19 | Medical Dental Advanced Technologies Group, L.L.C. | Dental and medical treatments and procedures |
US8470035B2 (en) | 2007-12-21 | 2013-06-25 | Microvention, Inc. | Hydrogel filaments for biomedical uses |
US10716573B2 (en) | 2008-05-01 | 2020-07-21 | Aneuclose | Janjua aneurysm net with a resilient neck-bridging portion for occluding a cerebral aneurysm |
US10028747B2 (en) | 2008-05-01 | 2018-07-24 | Aneuclose Llc | Coils with a series of proximally-and-distally-connected loops for occluding a cerebral aneurysm |
US9402707B2 (en) | 2008-07-22 | 2016-08-02 | Neuravi Limited | Clot capture systems and associated methods |
CN102202585B (en) | 2008-09-05 | 2014-04-02 | 帕尔萨脉管公司 | Systems and methods for supporting or occluding a physiological opening or cavity |
WO2011038291A1 (en) * | 2009-09-24 | 2011-03-31 | Microvention, Inc. | Injectable hydrogel filaments for biomedical uses |
AU2010313530B2 (en) * | 2009-10-26 | 2015-12-17 | Microvention, Inc. | Embolization device constructed from expansile polymer |
US9358140B1 (en) | 2009-11-18 | 2016-06-07 | Aneuclose Llc | Stent with outer member to embolize an aneurysm |
US9463036B2 (en) | 2010-10-22 | 2016-10-11 | Neuravi Limited | Clot engagement and removal system |
EP2683309B1 (en) | 2011-03-09 | 2021-04-21 | Neuravi Limited | A clot retrieval device for removing occlusive clot from a blood vessel |
US11259824B2 (en) | 2011-03-09 | 2022-03-01 | Neuravi Limited | Clot retrieval device for removing occlusive clot from a blood vessel |
US9456823B2 (en) | 2011-04-18 | 2016-10-04 | Terumo Corporation | Embolic devices |
KR102018035B1 (en) | 2011-06-03 | 2019-09-05 | 펄사 배스큘라, 아이엔씨. | Aneurysm devices with additional anchoring mechanisms and associated systems and methods |
EP4101399A1 (en) | 2011-08-05 | 2022-12-14 | Route 92 Medical, Inc. | System for treatment of acute ischemic stroke |
EP3738527A1 (en) | 2011-10-05 | 2020-11-18 | Pulsar Vascular, Inc. | Devices for enclosing an anatomical opening |
US9011884B2 (en) | 2012-04-18 | 2015-04-21 | Microvention, Inc. | Embolic devices |
EP2967824B1 (en) | 2013-03-12 | 2020-11-04 | Carnegie Mellon University | Coated vaso-occlusive device for treatment of aneurysms |
US10561509B2 (en) | 2013-03-13 | 2020-02-18 | DePuy Synthes Products, Inc. | Braided stent with expansion ring and method of delivery |
US10603157B2 (en) | 2013-03-13 | 2020-03-31 | DePuy Synthes Products, Inc. | Braid implant delivery and retraction device with distal engagement |
US9433429B2 (en) | 2013-03-14 | 2016-09-06 | Neuravi Limited | Clot retrieval devices |
PL2967611T3 (en) | 2013-03-14 | 2019-08-30 | Neuravi Limited | Devices for removal of acute blockages from blood vessels |
JP2016513505A (en) | 2013-03-14 | 2016-05-16 | ニューラヴィ・リミテッド | Clot collection device for removing obstructed clots from blood vessels |
CA2911415A1 (en) | 2013-06-26 | 2014-12-31 | Sonendo, Inc. | Apparatus and methods for filling teeth and root canals |
CN105814120B (en) | 2013-09-19 | 2019-07-05 | 泰尔茂株式会社 | Polymer beads |
AU2014321278B2 (en) | 2013-09-19 | 2016-11-10 | Microvention, Inc. | Polymer films |
WO2015070094A1 (en) | 2013-11-08 | 2015-05-14 | Microvention, Inc. | Polymer particles |
US9265512B2 (en) | 2013-12-23 | 2016-02-23 | Silk Road Medical, Inc. | Transcarotid neurovascular catheter |
US10285720B2 (en) | 2014-03-11 | 2019-05-14 | Neuravi Limited | Clot retrieval system for removing occlusive clot from a blood vessel |
US11154302B2 (en) | 2014-03-31 | 2021-10-26 | DePuy Synthes Products, Inc. | Aneurysm occlusion device |
US11076860B2 (en) | 2014-03-31 | 2021-08-03 | DePuy Synthes Products, Inc. | Aneurysm occlusion device |
US10124090B2 (en) | 2014-04-03 | 2018-11-13 | Terumo Corporation | Embolic devices |
WO2015167751A1 (en) * | 2014-04-29 | 2015-11-05 | Microvention, Inc. | Polymers |
CN110433326A (en) * | 2014-04-29 | 2019-11-12 | 微仙美国有限公司 | Polymer comprising activating agent |
US10441301B2 (en) | 2014-06-13 | 2019-10-15 | Neuravi Limited | Devices and methods for removal of acute blockages from blood vessels |
US10265086B2 (en) | 2014-06-30 | 2019-04-23 | Neuravi Limited | System for removing a clot from a blood vessel |
US9918718B2 (en) | 2014-08-08 | 2018-03-20 | DePuy Synthes Products, Inc. | Embolic coil delivery system with retractable mechanical release mechanism |
US10206796B2 (en) | 2014-08-27 | 2019-02-19 | DePuy Synthes Products, Inc. | Multi-strand implant with enhanced radiopacity |
US9782178B2 (en) | 2014-09-19 | 2017-10-10 | DePuy Synthes Products, Inc. | Vasculature occlusion device detachment system with tapered corewire and heater activated fiber detachment |
US11253278B2 (en) | 2014-11-26 | 2022-02-22 | Neuravi Limited | Clot retrieval system for removing occlusive clot from a blood vessel |
CN111743601A (en) | 2014-11-26 | 2020-10-09 | 尼尔拉维有限公司 | Thrombus retrieval device for removing obstructive thrombus from blood vessel |
US10617435B2 (en) | 2014-11-26 | 2020-04-14 | Neuravi Limited | Clot retrieval device for removing clot from a blood vessel |
US9616013B2 (en) * | 2014-12-24 | 2017-04-11 | L'oreal | Photo-activated hydrogels |
EP3237073B1 (en) * | 2014-12-24 | 2020-02-19 | L'Oréal | Photo-activated hydrogels |
US9637442B2 (en) * | 2014-12-24 | 2017-05-02 | L'oreal | Photo-activated hydrogels |
US11065019B1 (en) | 2015-02-04 | 2021-07-20 | Route 92 Medical, Inc. | Aspiration catheter systems and methods of use |
WO2016126974A1 (en) | 2015-02-04 | 2016-08-11 | Route 92 Medical, Inc. | Rapid aspiration thrombectomy system and method |
WO2016154592A1 (en) | 2015-03-26 | 2016-09-29 | Microvention, Inc. | Embiolic particles |
WO2016201250A1 (en) * | 2015-06-11 | 2016-12-15 | Microvention, Inc. | Expansile device for implantation |
WO2017019563A1 (en) | 2015-07-24 | 2017-02-02 | Route 92 Medical, Inc. | Anchoring delivery system and methods |
EP3346947A4 (en) | 2015-09-10 | 2019-07-24 | Ikonano Venture Partners, LLC | Polymeric electrospun embolization device and methods of use |
FI3393537T3 (en) | 2015-12-22 | 2024-08-20 | Access Vascular Inc | High strength biomedical materials |
KR101864674B1 (en) * | 2016-02-17 | 2018-06-05 | 한양대학교 산학협력단 | Patterned nanostructures by using stimuli-responsive soft nanoparticles and method for manufacturing the same |
CN113350655B (en) | 2016-02-24 | 2024-03-19 | 禾木(中国)生物工程有限公司 | Nerve vascular catheter with enhanced flexibility |
US10285710B2 (en) | 2016-06-01 | 2019-05-14 | DePuy Synthes Products, Inc. | Endovascular detachment system with flexible distal end and heater activated detachment |
CN109862835B (en) | 2016-08-17 | 2022-09-13 | 尼尔拉维有限公司 | Clot retrieval system for removing an occluded clot from a blood vessel |
US10076428B2 (en) | 2016-08-25 | 2018-09-18 | DePuy Synthes Products, Inc. | Expansion ring for a braided stent |
US11147572B2 (en) | 2016-09-06 | 2021-10-19 | Neuravi Limited | Clot retrieval device for removing occlusive clot from a blood vessel |
KR102241904B1 (en) | 2016-09-28 | 2021-04-16 | 테루모 가부시키가이샤 | Polymer particles |
US10292851B2 (en) | 2016-09-30 | 2019-05-21 | DePuy Synthes Products, Inc. | Self-expanding device delivery apparatus with dual function bump |
US10517708B2 (en) | 2016-10-26 | 2019-12-31 | DePuy Synthes Products, Inc. | Multi-basket clot capturing device |
CN110381855B (en) | 2017-01-06 | 2023-07-04 | 因赛普特有限责任公司 | Antithrombotic coating for aneurysm treatment devices |
CN110392591B (en) | 2017-01-10 | 2022-06-03 | 92号医疗公司 | Aspiration catheter system and method of use |
US10905853B2 (en) | 2017-01-17 | 2021-02-02 | DePuy Synthes Products, Inc. | System and method for delivering a catheter |
US10881497B2 (en) | 2017-01-26 | 2021-01-05 | DePuy Synthes Products, Inc. | Composite vascular flow diverter |
US10751066B2 (en) | 2017-02-23 | 2020-08-25 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
WO2018237166A1 (en) | 2017-06-21 | 2018-12-27 | Access Vascular, Inc | High strength porous materials incorporating water soluble polymers |
EP3699210A4 (en) * | 2017-10-18 | 2020-09-23 | FUJIFILM Corporation | Curable composition, film, cured product, and medical member |
WO2019078027A1 (en) | 2017-10-18 | 2019-04-25 | 富士フイルム株式会社 | Curable composition, film, cured product, and medical member |
US10806462B2 (en) | 2017-12-21 | 2020-10-20 | DePuy Synthes Products, Inc. | Implantable medical device detachment system with split tube and cylindrical coupling |
US10751065B2 (en) | 2017-12-22 | 2020-08-25 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
US10905430B2 (en) | 2018-01-24 | 2021-02-02 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
JP7248654B2 (en) | 2018-03-29 | 2023-03-29 | テルモ株式会社 | embolization material |
US10918390B2 (en) | 2018-03-30 | 2021-02-16 | DePuy Synthes Products, Inc. | Helical balloon assist device and method for using the same |
US10786259B2 (en) | 2018-03-30 | 2020-09-29 | DePuy Synthes Products, Inc. | Split balloon assist device and method for using the same |
US10806461B2 (en) | 2018-04-27 | 2020-10-20 | DePuy Synthes Products, Inc. | Implantable medical device detachment system with split tube |
WO2019212984A1 (en) | 2018-05-01 | 2019-11-07 | Imperative Care, Inc. | Devices and methods for removing obstructive material from an intravascular site |
US11395665B2 (en) | 2018-05-01 | 2022-07-26 | Incept, Llc | Devices and methods for removing obstructive material, from an intravascular site |
CN112423824B (en) | 2018-05-17 | 2023-02-21 | 92号医疗公司 | Aspiration catheter system and method of use |
US11596412B2 (en) | 2018-05-25 | 2023-03-07 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
US11058430B2 (en) | 2018-05-25 | 2021-07-13 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
US10939915B2 (en) | 2018-05-31 | 2021-03-09 | DePuy Synthes Products, Inc. | Aneurysm device and delivery system |
US10667833B2 (en) | 2018-06-08 | 2020-06-02 | Neuravi Limited | Guidewire with an atraumatic clot-circumventing configured distal end for use in an endovascular medical system |
US10898216B2 (en) | 2018-06-13 | 2021-01-26 | DePuy Synthes Products, Inc. | Vasculature obstruction capture device |
WO2020010310A1 (en) | 2018-07-06 | 2020-01-09 | Imperative Care, Inc. | Sealed neurovascular extendable catheter |
US11471582B2 (en) | 2018-07-06 | 2022-10-18 | Incept, Llc | Vacuum transfer tool for extendable catheter |
AU2019204522A1 (en) | 2018-07-30 | 2020-02-13 | DePuy Synthes Products, Inc. | Systems and methods of manufacturing and using an expansion ring |
US10905431B2 (en) | 2018-08-03 | 2021-02-02 | DePuy Synthes Products, Inc. | Spiral delivery system for embolic braid |
US10278848B1 (en) | 2018-08-06 | 2019-05-07 | DePuy Synthes Products, Inc. | Stent delivery with expansion assisting delivery wire |
US10456280B1 (en) | 2018-08-06 | 2019-10-29 | DePuy Synthes Products, Inc. | Systems and methods of using a braided implant |
US10813780B2 (en) | 2018-08-08 | 2020-10-27 | DePuy Synthes Products, Inc. | Intraluminal implant delivery system and method |
US11051825B2 (en) | 2018-08-08 | 2021-07-06 | DePuy Synthes Products, Inc. | Delivery system for embolic braid |
US10842498B2 (en) | 2018-09-13 | 2020-11-24 | Neuravi Limited | Systems and methods of restoring perfusion to a vessel |
BR102019019522A2 (en) | 2018-09-20 | 2020-04-07 | Depuy Synthes Products Inc | stent with conformed wires |
US11123077B2 (en) | 2018-09-25 | 2021-09-21 | DePuy Synthes Products, Inc. | Intrasaccular device positioning and deployment system |
US11406416B2 (en) | 2018-10-02 | 2022-08-09 | Neuravi Limited | Joint assembly for vasculature obstruction capture device |
US11253287B2 (en) | 2018-10-04 | 2022-02-22 | Neuravi Limited | Retrograde blood flow occlusion flushing device |
US11076861B2 (en) | 2018-10-12 | 2021-08-03 | DePuy Synthes Products, Inc. | Folded aneurysm treatment device and delivery method |
US11147562B2 (en) | 2018-12-12 | 2021-10-19 | DePuy Synthes Products, Inc. | Systems and methods for embolic implant detachment |
US11406392B2 (en) | 2018-12-12 | 2022-08-09 | DePuy Synthes Products, Inc. | Aneurysm occluding device for use with coagulating agents |
US11272939B2 (en) | 2018-12-18 | 2022-03-15 | DePuy Synthes Products, Inc. | Intrasaccular flow diverter for treating cerebral aneurysms |
US11039944B2 (en) | 2018-12-27 | 2021-06-22 | DePuy Synthes Products, Inc. | Braided stent system with one or more expansion rings |
US11134953B2 (en) | 2019-02-06 | 2021-10-05 | DePuy Synthes Products, Inc. | Adhesive cover occluding device for aneurysm treatment |
US11273285B2 (en) | 2019-02-07 | 2022-03-15 | DePuy Synthes Products, Inc. | Ancillary device for detaching implants |
EP4000540B1 (en) | 2019-03-04 | 2024-02-14 | Neuravi Limited | Actuated clot retrieval catheter |
US11382633B2 (en) | 2019-03-06 | 2022-07-12 | DePuy Synthes Products, Inc. | Strut flow diverter for cerebral aneurysms and methods for preventing strut entanglement |
US11337706B2 (en) | 2019-03-27 | 2022-05-24 | DePuy Synthes Products, Inc. | Aneurysm treatment device |
US11185334B2 (en) | 2019-03-28 | 2021-11-30 | DePuy Synthes Products, Inc. | Single lumen reduced profile occlusion balloon catheter |
US11766539B2 (en) | 2019-03-29 | 2023-09-26 | Incept, Llc | Enhanced flexibility neurovascular catheter |
US11051928B2 (en) | 2019-04-11 | 2021-07-06 | Neuravi Limited | Floating carotid filter |
US11607531B2 (en) | 2019-05-09 | 2023-03-21 | Neuravi Limited | Balloon catheter with venting of residual air in a proximal direction |
US11957855B2 (en) | 2019-05-09 | 2024-04-16 | Neuravi Limited | Balloon guide catheter with positive venting of residual air |
US11931522B2 (en) | 2019-05-09 | 2024-03-19 | Neuravi Limited | Inflation lumen kink protection and balloon profile |
US11571553B2 (en) | 2019-05-09 | 2023-02-07 | Neuravi Limited | Balloon guide catheter with thermally expandable material |
USD959659S1 (en) | 2019-05-10 | 2022-08-02 | DePuy Synthes Products, Inc. | Implant release handle |
US11497504B2 (en) | 2019-05-21 | 2022-11-15 | DePuy Synthes Products, Inc. | Aneurysm treatment with pushable implanted braid |
US10653425B1 (en) | 2019-05-21 | 2020-05-19 | DePuy Synthes Products, Inc. | Layered braided aneurysm treatment device |
US11602350B2 (en) | 2019-12-05 | 2023-03-14 | DePuy Synthes Products, Inc. | Intrasaccular inverting braid with highly flexible fill material |
US11413046B2 (en) | 2019-05-21 | 2022-08-16 | DePuy Synthes Products, Inc. | Layered braided aneurysm treatment device |
US11672542B2 (en) | 2019-05-21 | 2023-06-13 | DePuy Synthes Products, Inc. | Aneurysm treatment with pushable ball segment |
US11278292B2 (en) | 2019-05-21 | 2022-03-22 | DePuy Synthes Products, Inc. | Inverting braided aneurysm treatment system and method |
US11607226B2 (en) | 2019-05-21 | 2023-03-21 | DePuy Synthes Products, Inc. | Layered braided aneurysm treatment device with corrugations |
US11406403B2 (en) | 2019-06-14 | 2022-08-09 | Neuravi Limited | Visibility of mechanical thrombectomy device during diagnostic imaging |
US11109939B2 (en) | 2019-06-14 | 2021-09-07 | DePuy Synthes Products, Inc. | Intravascular devices with radiopaque body markers |
US11253265B2 (en) | 2019-06-18 | 2022-02-22 | DePuy Synthes Products, Inc. | Pull wire detachment for intravascular devices |
US11426174B2 (en) | 2019-10-03 | 2022-08-30 | DePuy Synthes Products, Inc. | Medical device delivery member with flexible stretch resistant mechanical release |
US11207494B2 (en) | 2019-07-03 | 2021-12-28 | DePuy Synthes Products, Inc. | Medical device delivery member with flexible stretch resistant distal portion |
US11266426B2 (en) | 2019-07-10 | 2022-03-08 | DePuy Synthes Products, Inc. | Streamlined treatment of clot removal, angioplasty and prevention of restenosis using a single integrated intravascular device |
US11266427B2 (en) | 2019-07-10 | 2022-03-08 | Neuravi Limited | Self-expanding intravascular medical device |
US11395675B2 (en) | 2019-07-11 | 2022-07-26 | DePuy Synthes Products, Inc. | Clot retriever cleaning for reinsertion |
US11529495B2 (en) | 2019-09-11 | 2022-12-20 | Neuravi Limited | Expandable mouth catheter |
US11439403B2 (en) | 2019-09-17 | 2022-09-13 | DePuy Synthes Products, Inc. | Embolic coil proximal connecting element and stretch resistant fiber |
CN110859999B (en) * | 2019-10-11 | 2021-02-02 | 南方医科大学 | Construction method of three-dimensional vascular network hydrogel |
WO2021076642A1 (en) | 2019-10-15 | 2021-04-22 | Imperative Care, Inc. | Systems and methods for multivariate stroke detection |
US11712231B2 (en) | 2019-10-29 | 2023-08-01 | Neuravi Limited | Proximal locking assembly design for dual stent mechanical thrombectomy device |
US11376013B2 (en) | 2019-11-18 | 2022-07-05 | DePuy Synthes Products, Inc. | Implant delivery system with braid cup formation |
US11628282B2 (en) | 2019-11-25 | 2023-04-18 | Neuravi Limited | No preparation balloon guide catheter |
US11779364B2 (en) | 2019-11-27 | 2023-10-10 | Neuravi Limited | Actuated expandable mouth thrombectomy catheter |
US11839725B2 (en) | 2019-11-27 | 2023-12-12 | Neuravi Limited | Clot retrieval device with outer sheath and inner catheter |
US11517340B2 (en) | 2019-12-03 | 2022-12-06 | Neuravi Limited | Stentriever devices for removing an occlusive clot from a vessel and methods thereof |
CN113365687A (en) | 2019-12-18 | 2021-09-07 | 因普瑞缇夫护理公司 | Method and system for treating venous thromboembolic disorders |
US11439799B2 (en) | 2019-12-18 | 2022-09-13 | Imperative Care, Inc. | Split dilator aspiration system |
US11457926B2 (en) | 2019-12-18 | 2022-10-04 | DePuy Synthes Products, Inc. | Implant having an intrasaccular section and intravascular section |
US11638637B2 (en) | 2019-12-18 | 2023-05-02 | Imperative Care, Inc. | Method of removing embolic material with thrombus engagement tool |
US11457922B2 (en) | 2020-01-22 | 2022-10-04 | DePuy Synthes Products, Inc. | Medical device delivery member with flexible stretch resistant distal portion |
US11992241B2 (en) | 2020-01-31 | 2024-05-28 | DePuy Synthes Products, Inc. | System to assist delivery of a mechanical intravascular treatment device |
US11957354B2 (en) | 2020-02-10 | 2024-04-16 | DePuy Synthes Products, Inc. | Aneurysm implant support device |
US11432822B2 (en) | 2020-02-14 | 2022-09-06 | DePuy Synthes Products, Inc. | Intravascular implant deployment system |
US11944327B2 (en) | 2020-03-05 | 2024-04-02 | Neuravi Limited | Expandable mouth aspirating clot retrieval catheter |
US11633198B2 (en) | 2020-03-05 | 2023-04-25 | Neuravi Limited | Catheter proximal joint |
CA3171899A1 (en) | 2020-03-10 | 2021-09-16 | Imperative Care, Inc. | Enhanced flexibility neurovascular catheter |
WO2021199884A1 (en) * | 2020-03-31 | 2021-10-07 | テルモ株式会社 | Embolization agent kit |
US11883043B2 (en) | 2020-03-31 | 2024-01-30 | DePuy Synthes Products, Inc. | Catheter funnel extension |
WO2021199883A1 (en) | 2020-03-31 | 2021-10-07 | テルモ株式会社 | Embolization agent |
US11759217B2 (en) | 2020-04-07 | 2023-09-19 | Neuravi Limited | Catheter tubular support |
US11717308B2 (en) | 2020-04-17 | 2023-08-08 | Neuravi Limited | Clot retrieval device for removing heterogeneous clots from a blood vessel |
US11730501B2 (en) | 2020-04-17 | 2023-08-22 | Neuravi Limited | Floating clot retrieval device for removing clots from a blood vessel |
US11871946B2 (en) | 2020-04-17 | 2024-01-16 | Neuravi Limited | Clot retrieval device for removing clot from a blood vessel |
US11523831B2 (en) | 2020-04-30 | 2022-12-13 | DePuy Synthes Products, Inc. | Intrasaccular flow diverter |
US11737771B2 (en) | 2020-06-18 | 2023-08-29 | Neuravi Limited | Dual channel thrombectomy device |
US11937836B2 (en) | 2020-06-22 | 2024-03-26 | Neuravi Limited | Clot retrieval system with expandable clot engaging framework |
US11395669B2 (en) | 2020-06-23 | 2022-07-26 | Neuravi Limited | Clot retrieval device with flexible collapsible frame |
US11439418B2 (en) | 2020-06-23 | 2022-09-13 | Neuravi Limited | Clot retrieval device for removing clot from a blood vessel |
CA3183979A1 (en) | 2020-06-30 | 2022-01-06 | Michael Bassett | Articles comprising markings and related methods |
US11951026B2 (en) | 2020-06-30 | 2024-04-09 | DePuy Synthes Products, Inc. | Implantable medical device detachment system with flexible braid section |
US11207497B1 (en) | 2020-08-11 | 2021-12-28 | Imperative Care, Inc. | Catheter with enhanced tensile strength |
US20220062609A1 (en) * | 2020-08-28 | 2022-03-03 | Bard Peripheral Vascular, Inc. | Compositions, Dispensers, and Methods Thereof for Establishing a Urine Passageway Through a Ureter |
US11864781B2 (en) | 2020-09-23 | 2024-01-09 | Neuravi Limited | Rotating frame thrombectomy device |
USD997355S1 (en) | 2020-10-07 | 2023-08-29 | Sonendo, Inc. | Dental treatment instrument |
US20240016706A1 (en) | 2020-11-04 | 2024-01-18 | Sonendo, Inc. | Materials for obturation |
US11826520B2 (en) | 2020-12-08 | 2023-11-28 | DePuy Synthes Products, Inc. | Catheter designs for enhanced column strength |
US11786698B2 (en) | 2020-12-08 | 2023-10-17 | DePuy Synthes Products, Inc. | Catheter with textured surface |
US11937837B2 (en) | 2020-12-29 | 2024-03-26 | Neuravi Limited | Fibrin rich / soft clot mechanical thrombectomy device |
US12029442B2 (en) | 2021-01-14 | 2024-07-09 | Neuravi Limited | Systems and methods for a dual elongated member clot retrieval apparatus |
US11872354B2 (en) | 2021-02-24 | 2024-01-16 | Neuravi Limited | Flexible catheter shaft frame with seam |
US12064130B2 (en) | 2021-03-18 | 2024-08-20 | Neuravi Limited | Vascular obstruction retrieval device having sliding cages pinch mechanism |
JP2024075522A (en) * | 2021-03-31 | 2024-06-04 | テルモ株式会社 | Embolization and method for producing embolization |
US11974764B2 (en) | 2021-06-04 | 2024-05-07 | Neuravi Limited | Self-orienting rotating stentriever pinching cells |
US11998213B2 (en) | 2021-07-14 | 2024-06-04 | DePuy Synthes Products, Inc. | Implant delivery with modified detachment feature and pull wire engagement |
US11937839B2 (en) | 2021-09-28 | 2024-03-26 | Neuravi Limited | Catheter with electrically actuated expandable mouth |
US12011186B2 (en) | 2021-10-28 | 2024-06-18 | Neuravi Limited | Bevel tip expandable mouth catheter with reinforcing ring |
US11751881B2 (en) | 2021-11-26 | 2023-09-12 | DePuy Synthes Products, Inc. | Securement wire withstanding forces during deployment of implantable intravascular treatment device using a delivery and detachment system |
US11844490B2 (en) | 2021-12-30 | 2023-12-19 | DePuy Synthes Products, Inc. | Suture linkage for inhibiting premature embolic implant deployment |
US11937824B2 (en) | 2021-12-30 | 2024-03-26 | DePuy Synthes Products, Inc. | Implant detachment systems with a modified pull wire |
US12011171B2 (en) | 2022-01-06 | 2024-06-18 | DePuy Synthes Products, Inc. | Systems and methods for inhibiting premature embolic implant deployment |
CN114533938A (en) * | 2022-02-25 | 2022-05-27 | 上海益思妙医疗器械有限公司 | Liquid embolic agent and application thereof in preparation of embolic agent |
US11937825B2 (en) | 2022-03-02 | 2024-03-26 | DePuy Synthes Products, Inc. | Hook wire for preventing premature embolic implant detachment |
US11937826B2 (en) | 2022-03-14 | 2024-03-26 | DePuy Synthes Products, Inc. | Proximal link wire for preventing premature implant detachment |
Family Cites Families (272)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3749085A (en) | 1970-06-26 | 1973-07-31 | J Willson | Vascular tissue removing device |
CS154391B1 (en) | 1970-09-10 | 1974-04-30 | ||
US4020829A (en) | 1975-10-23 | 1977-05-03 | Willson James K V | Spring guide wire with torque control for catheterization of blood vessels and method of using same |
US4509504A (en) | 1978-01-18 | 1985-04-09 | Medline Ab | Occlusion of body channels |
US4301803A (en) | 1978-10-06 | 1981-11-24 | Kuraray Co., Ltd. | Balloon catheter |
US4304232A (en) | 1979-03-14 | 1981-12-08 | Alza Corporation | Unit system having multiplicity of means for dispensing useful agent |
US4346712A (en) | 1979-04-06 | 1982-08-31 | Kuraray Company, Ltd. | Releasable balloon catheter |
SE419597B (en) | 1979-05-04 | 1981-08-17 | Medline Ab | DEVICE FOR TEMPORARY OR PERMANENT CONNECTION OF BODY CHANNELS OR SPACES OF HUMAN AND ANIMALS |
HU184722B (en) | 1980-02-18 | 1984-10-29 | Laszlo Lazar | Therapeutically suitable silicone rubber mixture and therapeuticaid |
US4493329A (en) | 1982-08-19 | 1985-01-15 | Lynn Crawford | Implantable electrode having different stiffening and curvature maintaining characteristics along its length |
GB8305797D0 (en) | 1983-03-02 | 1983-04-07 | Graham N B | Hydrogel-containing envelopes |
US4529739A (en) | 1984-07-24 | 1985-07-16 | The Dow Chemical Company | Foamed polymeric materials |
JPH0678460B2 (en) | 1985-05-01 | 1994-10-05 | 株式会社バイオマテリアル・ユニバース | Porous transparent polyvinyl alcohol gel |
US4795741A (en) | 1987-05-06 | 1989-01-03 | Biomatrix, Inc. | Compositions for therapeutic percutaneous embolization and the use thereof |
US4819637A (en) | 1987-09-01 | 1989-04-11 | Interventional Therapeutics Corporation | System for artificial vessel embolization and devices for use therewith |
US5165421A (en) | 1987-09-30 | 1992-11-24 | Lake Region Manufacturing Co., Inc. | Hollow lumen cable apparatus |
US5154705A (en) | 1987-09-30 | 1992-10-13 | Lake Region Manufacturing Co., Inc. | Hollow lumen cable apparatus |
US4932419A (en) | 1988-03-21 | 1990-06-12 | Boston Scientific Corporation | Multi-filar, cross-wound coil for medical devices |
US4951677A (en) | 1988-03-21 | 1990-08-28 | Prutech Research And Development Partnership Ii | Acoustic imaging catheter and the like |
US4994069A (en) | 1988-11-02 | 1991-02-19 | Target Therapeutics | Vaso-occlusion coil and method |
US5354290A (en) | 1989-05-31 | 1994-10-11 | Kimberly-Clark Corporation | Porous structure of an absorbent polymer |
DE69024363T2 (en) | 1989-10-03 | 1996-07-04 | Advanced Polymer Systems Inc | EDMABLE MACROPOROUS HYDROGEL PARTICLES AND THEIR PRODUCTION |
US5122136A (en) | 1990-03-13 | 1992-06-16 | The Regents Of The University Of California | Endovascular electrolytically detachable guidewire tip for the electroformation of thrombus in arteries, veins, aneurysms, vascular malformations and arteriovenous fistulas |
US6425893B1 (en) | 1990-03-13 | 2002-07-30 | The Regents Of The University Of California | Method and apparatus for fast electrolytic detachment of an implant |
JPH05507948A (en) | 1990-04-18 | 1993-11-11 | ユニバーシティ オブ ユタ リサーチ ファウンデーション | Colon-targeted oral drug dosage forms based on cross-linked hydrogels containing azo bonds and exhibiting pH-dependent swelling |
US5163952A (en) | 1990-09-14 | 1992-11-17 | Michael Froix | Expandable polymeric stent with memory and delivery apparatus and method |
US5133731A (en) | 1990-11-09 | 1992-07-28 | Catheter Research, Inc. | Embolus supply system and method |
US5120349A (en) | 1990-12-07 | 1992-06-09 | Landec Labs, Inc. | Microcapsule having temperature-dependent permeability profile |
US5129180A (en) | 1990-12-07 | 1992-07-14 | Landec Labs, Inc. | Temperature sensitive seed germination control |
US6524274B1 (en) | 1990-12-28 | 2003-02-25 | Scimed Life Systems, Inc. | Triggered release hydrogel drug delivery system |
DE4104702C2 (en) | 1991-02-15 | 1996-01-18 | Malte Neuss | Implants for organ pathways in spiral form |
US5217484A (en) | 1991-06-07 | 1993-06-08 | Marks Michael P | Retractable-wire catheter device and method |
CA2117088A1 (en) | 1991-09-05 | 1993-03-18 | David R. Holmes | Flexible tubular device for use in medical applications |
US5226911A (en) | 1991-10-02 | 1993-07-13 | Target Therapeutics | Vasoocclusion coil with attached fibrous element(s) |
US5304194A (en) | 1991-10-02 | 1994-04-19 | Target Therapeutics | Vasoocclusion coil with attached fibrous element(s) |
JP3356447B2 (en) | 1991-10-16 | 2002-12-16 | テルモ株式会社 | Vascular lesion embolic material composed of dried polymer gel |
US5258042A (en) | 1991-12-16 | 1993-11-02 | Henry Ford Health System | Intravascular hydrogel implant |
WO1993012877A1 (en) | 1991-12-20 | 1993-07-08 | Allied-Signal Inc. | Low density materials having high surface areas and articles formed therefrom for use in the recovery of metals |
US5573934A (en) | 1992-04-20 | 1996-11-12 | Board Of Regents, The University Of Texas System | Gels for encapsulation of biological materials |
US5514379A (en) | 1992-08-07 | 1996-05-07 | The General Hospital Corporation | Hydrogel compositions and methods of use |
US5443478A (en) | 1992-09-02 | 1995-08-22 | Board Of Regents, The University Of Texas System | Multi-element intravascular occlusion device |
US5469867A (en) | 1992-09-02 | 1995-11-28 | Landec Corporation | Cast-in place thermoplastic channel occluder |
WO1994006460A1 (en) | 1992-09-21 | 1994-03-31 | Vitaphore Corporation | Embolization plugs for blood vessels |
US5312415A (en) | 1992-09-22 | 1994-05-17 | Target Therapeutics, Inc. | Assembly for placement of embolic coils using frictional placement |
US5350397A (en) | 1992-11-13 | 1994-09-27 | Target Therapeutics, Inc. | Axially detachable embolic coil assembly |
US5447727A (en) | 1992-10-14 | 1995-09-05 | The Dow Chemical Company | Water-absorbent polymer having improved properties |
US5382259A (en) | 1992-10-26 | 1995-01-17 | Target Therapeutics, Inc. | Vasoocclusion coil with attached tubular woven or braided fibrous covering |
US5382260A (en) | 1992-10-30 | 1995-01-17 | Interventional Therapeutics Corp. | Embolization device and apparatus including an introducer cartridge and method for delivering the same |
US5690666A (en) | 1992-11-18 | 1997-11-25 | Target Therapeutics, Inc. | Ultrasoft embolism coils and process for using them |
AU677808B2 (en) | 1992-12-01 | 1997-05-08 | Intella Interventional Systems, Inc. | Vibratory element for crossing stenoses |
US5698189A (en) | 1993-03-23 | 1997-12-16 | Focal, Inc. | Method for local application of polymeric material to tissue |
US5554147A (en) | 1994-02-01 | 1996-09-10 | Caphco, Inc. | Compositions and devices for controlled release of active ingredients |
US5883705A (en) | 1994-04-12 | 1999-03-16 | The Board Of Trustees Of The Leland Stanford, Jr. University | Atomic force microscope for high speed imaging including integral actuator and sensor |
US5483022A (en) | 1994-04-12 | 1996-01-09 | Ventritex, Inc. | Implantable conductor coil formed from cabled composite wire |
US5573994A (en) | 1994-05-13 | 1996-11-12 | University Of Cincinnati | Superabsorbent foams, and method for producing the same |
JP2535785B2 (en) | 1994-06-03 | 1996-09-18 | 工業技術院長 | Vascular embolic agent |
US5549624A (en) | 1994-06-24 | 1996-08-27 | Target Therapeutics, Inc. | Fibered vasooclusion coils |
ES2185707T5 (en) | 1994-07-08 | 2007-05-01 | Ev3 Inc. | INTRAVASCULAR FILTRATION DEVICE. |
US5582610A (en) | 1994-09-30 | 1996-12-10 | Circon Corporation | Grooved slider electrode for a resectoscope |
US5690671A (en) | 1994-12-13 | 1997-11-25 | Micro Interventional Systems, Inc. | Embolic elements and methods and apparatus for their delivery |
US5814062A (en) | 1994-12-22 | 1998-09-29 | Target Therapeutics, Inc. | Implant delivery assembly with expandable coupling/decoupling mechanism |
US5578074A (en) | 1994-12-22 | 1996-11-26 | Target Therapeutics, Inc. | Implant delivery method and assembly |
DE69632392T2 (en) | 1995-01-27 | 2004-09-16 | Scimed Life Systems, Inc., Maple Grove | Embolisation |
US5634936A (en) | 1995-02-06 | 1997-06-03 | Scimed Life Systems, Inc. | Device for closing a septal defect |
US5651979A (en) | 1995-03-30 | 1997-07-29 | Gel Sciences, Inc. | Apparatus and method for delivering a biologically active compound into a biological environment |
US5750585A (en) * | 1995-04-04 | 1998-05-12 | Purdue Research Foundation | Super absorbent hydrogel foams |
US5645558A (en) | 1995-04-20 | 1997-07-08 | Medical University Of South Carolina | Anatomically shaped vasoocclusive device and method of making the same |
US6171326B1 (en) | 1998-08-27 | 2001-01-09 | Micrus Corporation | Three dimensional, low friction vasoocclusive coil, and method of manufacture |
US5766160A (en) | 1995-06-06 | 1998-06-16 | Target Therapeutics, Inc. | Variable stiffness coils |
US5624461A (en) | 1995-06-06 | 1997-04-29 | Target Therapeutics, Inc. | Three dimensional in-filling vaso-occlusive coils |
US6705323B1 (en) | 1995-06-07 | 2004-03-16 | Conceptus, Inc. | Contraceptive transcervical fallopian tube occlusion devices and methods |
US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US5725568A (en) | 1995-06-27 | 1998-03-10 | Scimed Life Systems, Inc. | Method and device for recanalizing and grafting arteries |
DE69610875T2 (en) | 1995-06-30 | 2001-03-01 | Target Therapeutics, Inc. | Expansion-resistant vaso-occlusive spiral |
US5853418A (en) | 1995-06-30 | 1998-12-29 | Target Therapeutics, Inc. | Stretch resistant vaso-occlusive coils (II) |
US5582619A (en) | 1995-06-30 | 1996-12-10 | Target Therapeutics, Inc. | Stretch resistant vaso-occlusive coils |
US6013084A (en) | 1995-06-30 | 2000-01-11 | Target Therapeutics, Inc. | Stretch resistant vaso-occlusive coils (II) |
US5580568A (en) | 1995-07-27 | 1996-12-03 | Micro Therapeutics, Inc. | Cellulose diacetate compositions for use in embolizing blood vessels |
US5667767A (en) | 1995-07-27 | 1997-09-16 | Micro Therapeutics, Inc. | Compositions for use in embolizing blood vessels |
JPH11510837A (en) * | 1995-07-28 | 1999-09-21 | フォーカル,インコーポレイテッド | Multi-block biodegradable hydrogels for use as controlled release and tissue treatment agents for drug delivery |
US5658308A (en) | 1995-12-04 | 1997-08-19 | Target Therapeutics, Inc. | Bioactive occlusion coil |
US5752974A (en) | 1995-12-18 | 1998-05-19 | Collagen Corporation | Injectable or implantable biomaterials for filling or blocking lumens and voids of the body |
DE69623597T2 (en) * | 1995-12-19 | 2003-05-22 | Bracco Research S.A., Carouge | COMPOSITIONS CONTAINING TRICODOBENZENE POLYMERS FOR IMAGING THE GASTROINTESTINAL TRACT |
US5749894A (en) | 1996-01-18 | 1998-05-12 | Target Therapeutics, Inc. | Aneurysm closure method |
US5702361A (en) | 1996-01-31 | 1997-12-30 | Micro Therapeutics, Inc. | Method for embolizing blood vessels |
US5792154A (en) | 1996-04-10 | 1998-08-11 | Target Therapeutics, Inc. | Soft-ended fibered micro vaso-occlusive devices |
DE69718180T2 (en) | 1996-05-31 | 2003-08-21 | Micro Therapeutics, Inc. | COMPOSITIONS FOR USE IN EMBOLIZING BLOOD VESSELS |
WO1998001421A1 (en) | 1996-07-10 | 1998-01-15 | University Of Utah Research Foundation | pH SENSITIVE HYDROGELS WITH ADJUSTABLE SWELLING KINETICS FOR COLON-SPECIFIC DELIVERY OF PEPTIDES AND PROTEINS |
US5980514A (en) | 1996-07-26 | 1999-11-09 | Target Therapeutics, Inc. | Aneurysm closure device assembly |
US6096034A (en) | 1996-07-26 | 2000-08-01 | Target Therapeutics, Inc. | Aneurysm closure device assembly |
US5830178A (en) | 1996-10-11 | 1998-11-03 | Micro Therapeutics, Inc. | Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide |
US5695480A (en) | 1996-07-29 | 1997-12-09 | Micro Therapeutics, Inc. | Embolizing compositions |
US5823198A (en) | 1996-07-31 | 1998-10-20 | Micro Therapeutics, Inc. | Method and apparatus for intravasculer embolization |
US6706690B2 (en) | 1999-06-10 | 2004-03-16 | Baxter Healthcare Corporation | Hemoactive compositions and methods for their manufacture and use |
WO1998012274A1 (en) | 1996-09-23 | 1998-03-26 | Chandrashekar Pathak | Methods and devices for preparing protein concentrates |
US5690667A (en) | 1996-09-26 | 1997-11-25 | Target Therapeutics | Vasoocclusion coil having a polymer tip |
US5863551A (en) | 1996-10-16 | 1999-01-26 | Organogel Canada Ltee | Implantable polymer hydrogel for therapeutic uses |
US5785642A (en) | 1996-10-18 | 1998-07-28 | Micro Therapeutics, Inc. | Methods for treating urinary incontinence in mammals |
US5672634A (en) | 1996-12-23 | 1997-09-30 | Isp Investments Inc. | Crosslinked PVP-I2 foam product |
US5853419A (en) | 1997-03-17 | 1998-12-29 | Surface Genesis, Inc. | Stent |
EP0975328A1 (en) | 1997-04-02 | 2000-02-02 | Purdue Research Foundation | Method for oral delivery of proteins |
US6399886B1 (en) | 1997-05-02 | 2002-06-04 | General Science & Technology Corp. | Multifilament drawn radiopaque high elastic cables and methods of making the same |
DE19724796A1 (en) | 1997-06-06 | 1998-12-10 | Max Delbrueck Centrum | Antitumor therapy agents |
JP2002503991A (en) | 1997-06-13 | 2002-02-05 | マイクロ・テラピューティクス・インコーポレーテッド | Syringe and luer hub having novel shape and method of forming embolus |
US6860893B2 (en) | 1997-08-29 | 2005-03-01 | Boston Scientific Scimed, Inc. | Stable coil designs |
US6066149A (en) | 1997-09-30 | 2000-05-23 | Target Therapeutics, Inc. | Mechanical clot treatment device with distal filter |
US6004573A (en) | 1997-10-03 | 1999-12-21 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
US6511468B1 (en) | 1997-10-17 | 2003-01-28 | Micro Therapeutics, Inc. | Device and method for controlling injection of liquid embolic composition |
US6146373A (en) | 1997-10-17 | 2000-11-14 | Micro Therapeutics, Inc. | Catheter system and method for injection of a liquid embolic composition and a solidification agent |
JP2001522629A (en) | 1997-11-07 | 2001-11-20 | サルヴィアック・リミテッド | Medical insertable occlusive device |
US6159165A (en) | 1997-12-05 | 2000-12-12 | Micrus Corporation | Three dimensional spherical micro-coils manufactured from radiopaque nickel-titanium microstrand |
US6168570B1 (en) | 1997-12-05 | 2001-01-02 | Micrus Corporation | Micro-strand cable with enhanced radiopacity |
US6136015A (en) | 1998-08-25 | 2000-10-24 | Micrus Corporation | Vasoocclusive coil |
US7070607B2 (en) | 1998-01-27 | 2006-07-04 | The Regents Of The University Of California | Bioabsorbable polymeric implants and a method of using the same to create occlusions |
WO1999044538A1 (en) | 1998-01-27 | 1999-09-10 | The Regents Of The University Of California | Biodegradable polymer/protein based coils for intralumenal implants |
US5935145A (en) | 1998-02-13 | 1999-08-10 | Target Therapeutics, Inc. | Vaso-occlusive device with attached polymeric materials |
US6063100A (en) | 1998-03-10 | 2000-05-16 | Cordis Corporation | Embolic coil deployment system with improved embolic coil |
US6015424A (en) | 1998-04-28 | 2000-01-18 | Microvention, Inc. | Apparatus and method for vascular embolization |
US6113629A (en) | 1998-05-01 | 2000-09-05 | Micrus Corporation | Hydrogel for the therapeutic treatment of aneurysms |
US5980550A (en) | 1998-06-18 | 1999-11-09 | Target Therapeutics, Inc. | Water-soluble coating for bioactive vasoocclusive devices |
US6051607A (en) | 1998-07-02 | 2000-04-18 | Micro Therapeutics, Inc. | Vascular embolizing compositions comprising ethyl lactate and methods for their use |
KR20000012970A (en) | 1998-08-03 | 2000-03-06 | 김효근 | Ph sensing polymer containing sulfonamide group and preparing it |
US6093199A (en) | 1998-08-05 | 2000-07-25 | Endovascular Technologies, Inc. | Intra-luminal device for treatment of body cavities and lumens and method of use |
US6605294B2 (en) | 1998-08-14 | 2003-08-12 | Incept Llc | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
EP1105169A1 (en) | 1998-08-20 | 2001-06-13 | Cook Incorporated | Coated implantable medical device |
US5952232A (en) | 1998-09-17 | 1999-09-14 | Rothman; James Edward | Expandible microparticle intracellular delivery system |
US6187024B1 (en) | 1998-11-10 | 2001-02-13 | Target Therapeutics, Inc. | Bioactive coating for vaso-occlusive devices |
US6245740B1 (en) | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
EP1031354A3 (en) * | 1999-01-19 | 2003-02-05 | Rohm And Haas Company | Polymeric MRI Contrast agents |
US6179857B1 (en) | 1999-02-22 | 2001-01-30 | Cordis Corporation | Stretch resistant embolic coil with variable stiffness |
US6303100B1 (en) | 1999-03-19 | 2001-10-16 | Micro Therapeutics, Inc. | Methods for inhibiting the formation of potential endoleaks associated with endovascular repair of abdominal aortic aneurysms |
US6333020B1 (en) | 1999-05-13 | 2001-12-25 | Micro Therapeutics, Inc. | Methods for treating AVM's using radio active compositions |
EP1185223A1 (en) | 1999-05-21 | 2002-03-13 | Micro Therapeutics, Inc. | Methods for delivering in vivo uniform dispersed embolic compositions of high viscosity |
EP1206287B1 (en) | 1999-05-21 | 2008-12-17 | Micro Therapeutics, Inc. | High viscosity embolizing compositions |
US7018365B2 (en) | 1999-05-21 | 2006-03-28 | Micro Therapeutics, Inc. | Threaded syringe with quick stop |
WO2000071196A1 (en) | 1999-05-21 | 2000-11-30 | Micro Therapeutics, Inc. | Interface needle and method for creating a blunt interface between delivered liquids |
US6645167B1 (en) | 1999-05-21 | 2003-11-11 | Micro Therapeutics, Inc. | Methods for embolizing vascular sites with an embolizing composition |
US20020169473A1 (en) | 1999-06-02 | 2002-11-14 | Concentric Medical, Inc. | Devices and methods for treating vascular malformations |
US6280457B1 (en) | 1999-06-04 | 2001-08-28 | Scimed Life Systems, Inc. | Polymer covered vaso-occlusive devices and methods of producing such devices |
US6521431B1 (en) | 1999-06-22 | 2003-02-18 | Access Pharmaceuticals, Inc. | Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments |
US6312421B1 (en) | 1999-07-23 | 2001-11-06 | Neurovasx, Inc. | Aneurysm embolization material and device |
US6602261B2 (en) | 1999-10-04 | 2003-08-05 | Microvention, Inc. | Filamentous embolic device with expansile elements |
US6238403B1 (en) | 1999-10-04 | 2001-05-29 | Microvention, Inc. | Filamentous embolic device with expansible elements |
JP4856339B2 (en) | 1999-10-26 | 2012-01-18 | 泰彦 田畑 | Vascular embolization material comprising hydrogel and treatment method using the same |
US6623450B1 (en) | 1999-12-17 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | System for blocking the passage of emboli through a body vessel |
EP1263803B1 (en) * | 2000-03-13 | 2007-09-19 | BioCure, Inc. | Embolic compositions |
US7338657B2 (en) | 2001-03-15 | 2008-03-04 | Biosphere Medical, Inc. | Injectable microspheres for tissue construction |
US6656200B2 (en) | 2000-04-07 | 2003-12-02 | Collagen Matrix, Inc. | Embolization device |
US6599448B1 (en) | 2000-05-10 | 2003-07-29 | Hydromer, Inc. | Radio-opaque polymeric compositions |
US7291673B2 (en) | 2000-06-02 | 2007-11-06 | Eidgenossiche Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
WO2002005731A1 (en) | 2000-07-18 | 2002-01-24 | Teitelbaum George P | Biocompatible, expansile material and stent |
US6723108B1 (en) | 2000-09-18 | 2004-04-20 | Cordis Neurovascular, Inc | Foam matrix embolization device |
US8313504B2 (en) | 2000-09-18 | 2012-11-20 | Cordis Corporation | Foam matrix embolization device |
US7033374B2 (en) | 2000-09-26 | 2006-04-25 | Microvention, Inc. | Microcoil vaso-occlusive device with multi-axis secondary configuration |
WO2002030487A2 (en) | 2000-10-11 | 2002-04-18 | Micro Thereapeutics, Inc. | Methods for treating aneurysms |
US6537569B2 (en) | 2001-02-14 | 2003-03-25 | Microvention, Inc. | Radiation cross-linked hydrogels |
US6503244B2 (en) | 2001-03-07 | 2003-01-07 | Micro Therapeutics, Inc. | High pressure injection system |
US6878384B2 (en) | 2001-03-13 | 2005-04-12 | Microvention, Inc. | Hydrogels that undergo volumetric expansion in response to changes in their environment and their methods of manufacture and use |
ATE516759T1 (en) | 2001-05-29 | 2011-08-15 | Microvention Inc | METHOD FOR PRODUCING EXPANDABLE FILAMENTOUS EMBOLIZATION DEVICES |
US8101196B2 (en) | 2001-06-26 | 2012-01-24 | Biointeractions, Ltd. | Polysaccharide biomaterials and methods of use thereof |
EP2292292B1 (en) | 2001-09-04 | 2018-04-11 | Covidien LP | Occlusion catheter having compliant balloon for use with complex vasculature |
WO2003043552A1 (en) * | 2001-11-16 | 2003-05-30 | Biocure, Inc. | Methods for initiating in situ formation of hydrogels |
EP1465668A2 (en) | 2002-01-14 | 2004-10-13 | Micro Therapeutics, Inc. | Methods for embolizing aneurysmal sites with a high viscosity embolizing composition |
DE60325827D1 (en) | 2002-02-21 | 2009-03-05 | Encelle Inc | NETWORKED BIOACTIVE HYDROGEL MATRICES |
WO2003089506A1 (en) | 2002-04-22 | 2003-10-30 | Purdue Research Foundation | Hydrogels having enhanced elasticity and mechanical strength properties |
US7008979B2 (en) | 2002-04-30 | 2006-03-07 | Hydromer, Inc. | Coating composition for multiple hydrophilic applications |
US7459142B2 (en) | 2002-06-06 | 2008-12-02 | Micro Therapeutics, Inc. | High viscosity embolizing compositions comprising prepolymers |
US20040039670A1 (en) | 2002-06-20 | 2004-02-26 | Fung Ka Shun Kevin | Method and system for improving the liquidity of transactions |
US20040006354A1 (en) | 2002-07-02 | 2004-01-08 | Dean Schaefer | Coaxial stretch-resistant vaso-occlusive device |
US7608058B2 (en) | 2002-07-23 | 2009-10-27 | Micrus Corporation | Stretch resistant therapeutic device |
US7067606B2 (en) | 2002-07-30 | 2006-06-27 | University Of Connecticut | Nonionic telechelic polymers incorporating polyhedral oligosilsesquioxane (POSS) and uses thereof |
US20050171572A1 (en) | 2002-07-31 | 2005-08-04 | Microvention, Inc. | Multi-layer coaxial vaso-occlusive device |
JP4425789B2 (en) | 2002-07-31 | 2010-03-03 | マイクロベンション インコーポレイテッド | Three-element coaxial vessel occlusion device |
EP1551489B1 (en) | 2002-10-10 | 2009-12-09 | Micro Therapeutics, Inc. | Wire braid-reinforced microcatheter |
US7588825B2 (en) | 2002-10-23 | 2009-09-15 | Boston Scientific Scimed, Inc. | Embolic compositions |
US20040115164A1 (en) * | 2002-12-17 | 2004-06-17 | Pierce Ryan K. | Soft filament occlusive device delivery system |
US7312301B2 (en) | 2002-12-31 | 2007-12-25 | Nektar Therapeutics Al, Corporation | Methods for the formation of hydrogels using thiosulfonate compositions and uses thereof |
EP1435248A1 (en) | 2003-01-02 | 2004-07-07 | Vesalius N.V. | Composition for in vivo vessel repair |
US20050043585A1 (en) | 2003-01-03 | 2005-02-24 | Arindam Datta | Reticulated elastomeric matrices, their manufacture and use in implantable devices |
EP1599258B1 (en) | 2003-02-26 | 2008-08-06 | Micro Therapeutics, Inc. | Fumed silica embolic compositions |
DE602004020874D1 (en) | 2003-03-07 | 2009-06-10 | Micro Therapeutics Inc | COMPOSITIONS CONTAINED HIGH CONCENTRATION OF CONTRAST ELEMENTS FOR EMBOLIZING BLOOD CONTAINERS |
CN106215226A (en) | 2003-03-24 | 2016-12-14 | 健赞公司 | Utilize the temporary embolization of inverse thermosensitive polymers |
EP1606009A2 (en) * | 2003-03-25 | 2005-12-21 | BioCure, Inc. | Hydrogel string medical device |
GB0307834D0 (en) * | 2003-04-04 | 2003-05-14 | Ta Contrast Ab | Composition |
US7641643B2 (en) | 2003-04-15 | 2010-01-05 | Abbott Cardiovascular Systems Inc. | Methods and compositions to treat myocardial conditions |
ES2440654T3 (en) | 2003-05-05 | 2014-01-29 | Ben-Gurion University Of The Negev Research And Development Authority | Injectable crosslinked polymeric preparations and uses thereof |
US20050119687A1 (en) * | 2003-09-08 | 2005-06-02 | Dacey Ralph G.Jr. | Methods of, and materials for, treating vascular defects with magnetically controllable hydrogels |
JP5186109B2 (en) | 2003-09-25 | 2013-04-17 | ラトガース,ザ ステート ユニバーシティ | Polymer products that are essentially radiopaque for embolization treatment |
US7901770B2 (en) | 2003-11-04 | 2011-03-08 | Boston Scientific Scimed, Inc. | Embolic compositions |
US20050175709A1 (en) | 2003-12-11 | 2005-08-11 | Baty Ace M.Iii | Therapeutic microparticles |
EP2289567A3 (en) | 2003-12-22 | 2011-06-22 | Regentis Biomaterials Ltd. | Matrix comprising naturally-occurring crosslinked protein backbone |
US7736671B2 (en) | 2004-03-02 | 2010-06-15 | Boston Scientific Scimed, Inc. | Embolization |
US8173176B2 (en) | 2004-03-30 | 2012-05-08 | Boston Scientific Scimed, Inc. | Embolization |
BRPI0510477B1 (en) | 2004-04-28 | 2023-01-17 | Angiotech Biomaterials Corporation | METHOD FOR FORMING A GEL AND DEVICE FOR USE IN MEDICAL APPLICATIONS |
EP1791590B1 (en) | 2004-08-25 | 2015-07-15 | Microvention, Inc. | Thermal detachment system for implantable devices |
EP1796693A2 (en) | 2004-08-26 | 2007-06-20 | Chandrashekhar P. Pathak | Implantable tissue compositions and method |
US20060074370A1 (en) | 2004-09-24 | 2006-04-06 | Medennium, Inc. | Ocular occluder and method of insertion |
CA2579612A1 (en) | 2004-09-24 | 2006-04-06 | Biosphere Medical, Inc. | Microspheres capable of binding radioisotopes, optionally comprising metallic microparticles, and methods of use thereof |
US8075906B2 (en) | 2005-02-01 | 2011-12-13 | Boston Scientific Scimed, Inc. | Medical devices having polymeric regions with copolymers containing hydrocarbon and heteroatom-containing monomeric species |
WO2007016371A2 (en) | 2005-07-28 | 2007-02-08 | Akina, Inc. | Readily shapeable xerogels having controllably delayed swelling properties |
US20070026039A1 (en) | 2005-07-29 | 2007-02-01 | Drumheller Paul D | Composite self-cohered web materials |
EP1996243B1 (en) | 2006-01-11 | 2014-04-23 | HyperBranch Medical Technology, Inc. | Crosslinked gels comprising polyalkyleneimines, and their uses as medical devices |
WO2007090130A2 (en) | 2006-01-30 | 2007-08-09 | Surgica Corporation | Porous intravascular embolization particles and related methods |
US7732539B2 (en) | 2006-02-16 | 2010-06-08 | National Science Foundation | Modified acrylic block copolymers for hydrogels and pressure sensitive wet adhesives |
US20070202046A1 (en) | 2006-02-24 | 2007-08-30 | Vipul Dave | Implantable device formed from polymer blends |
US20070224234A1 (en) | 2006-03-22 | 2007-09-27 | Mark Steckel | Medical devices having biodegradable polymeric regions |
US8795709B2 (en) | 2006-03-29 | 2014-08-05 | Incept Llc | Superabsorbent, freeze dried hydrogels for medical applications |
WO2007114823A1 (en) | 2006-04-06 | 2007-10-11 | Reva Medical, Inc. | Embolic prosthesis for treatment of vascular aneurysm |
US8252339B2 (en) | 2006-04-11 | 2012-08-28 | Massachusetts Institute Of Technology | Medical treatment applications of swellable and deformable microspheres |
WO2007127198A2 (en) | 2006-04-24 | 2007-11-08 | Incept, Llc | Protein crosslinkers, crosslinking methods and applications thereof |
US20070288084A1 (en) | 2006-06-09 | 2007-12-13 | Medlogics Device Corporation | Implantable Stent with Degradable Portions |
JP2010500917A (en) | 2006-06-15 | 2010-01-14 | マイクロベンション, インコーポレイテッド | Embolization device composed of expandable polymer |
JP2009542671A (en) | 2006-06-28 | 2009-12-03 | サーモディクス,インコーポレイティド | Active agent elution matrix containing fine particles |
US20080019921A1 (en) | 2006-06-30 | 2008-01-24 | Invitrogen Corporation | Uniform fluorescent microsphere with hydrophobic surfaces |
MX2009000046A (en) | 2006-07-06 | 2009-06-05 | Abbott Respiratory Llc | Superporous hydrogels for heavy-duty applications. |
US8414927B2 (en) | 2006-11-03 | 2013-04-09 | Boston Scientific Scimed, Inc. | Cross-linked polymer particles |
CN103169571B (en) | 2006-11-09 | 2015-04-15 | 凯希特许有限公司 | Porous bioresorbable dressing including microspheres and methods for making same |
EP2099845B1 (en) | 2006-11-27 | 2020-12-23 | Actamax Surgical Materials LLC | Multi-functional polyalkylene oxides, hydrogels and tissue adhesives |
EP2152779B1 (en) | 2007-05-11 | 2018-10-24 | Aeris Therapeutics, LLC | Lung volume reduction therapy using crosslinked non-natural polymers |
WO2008153994A2 (en) | 2007-06-11 | 2008-12-18 | Kieran Murphy | Method and kit for cyst aspiration and treatment |
GB0711952D0 (en) | 2007-06-20 | 2007-08-01 | King S College London | Microspheres |
US7887846B2 (en) | 2007-08-07 | 2011-02-15 | E. I. Du Pont De Nemours And Company | Process for preparation of swellable and degradable microspheres |
EP2178949B1 (en) | 2007-08-14 | 2017-12-13 | Cook Medical Technologies LLC | Photoactivated crosslinking of a protein or peptide |
US20090048659A1 (en) | 2007-08-17 | 2009-02-19 | Boston Scientific Scimed, Inc. | Medical devices having sol-gel derived ceramic regions with molded submicron surface features |
WO2009029443A2 (en) | 2007-08-24 | 2009-03-05 | E. I. Du Pont De Nemours And Company | Method for embolization using liquid embolic materials |
WO2009038783A1 (en) | 2007-09-19 | 2009-03-26 | Surmodics, Inc. | Biocompatible foams, systems, and methods |
WO2009042191A1 (en) | 2007-09-25 | 2009-04-02 | Surmodics, Inc. | Durable swellable hydrogel matrix, method for preparation and method for encapsulation |
US8246998B2 (en) | 2007-11-01 | 2012-08-21 | Boston Scientific Scimed, Inc. | Injectable biodegradable particles |
US8999323B2 (en) | 2007-11-23 | 2015-04-07 | Technische Universität Wien | Composition that can be cured by polymerisation for the production of biodegradable, biocompatible, cross-linkable polymers on the basis of polyvinyl alcohol |
WO2009110939A2 (en) | 2007-12-10 | 2009-09-11 | Massachusetts Institute Of Technology | Drug delivery system for pharmaceuticals and radiation |
US8470035B2 (en) | 2007-12-21 | 2013-06-25 | Microvention, Inc. | Hydrogel filaments for biomedical uses |
US20090181068A1 (en) | 2008-01-14 | 2009-07-16 | Dunn Richard L | Low Viscosity Liquid Polymeric Delivery System |
WO2009108760A2 (en) | 2008-02-26 | 2009-09-03 | Board Of Regents, The University Of Texas System | Dendritic macroporous hydrogels prepared by crystal templating |
US8324292B2 (en) | 2008-02-29 | 2012-12-04 | Ethicon, Inc. | Medically acceptable formulation of a diisocyanate terminated macromer for use as an internal adhesive or sealant |
EP2103313A1 (en) | 2008-03-19 | 2009-09-23 | Koninklijke Philips Electronics N.V. | Method for the synthesis of hollow spheres |
US8128983B2 (en) | 2008-04-11 | 2012-03-06 | Abbott Cardiovascular Systems Inc. | Coating comprising poly(ethylene glycol)-poly(lactide-glycolide-caprolactone) interpenetrating network |
US8207264B2 (en) | 2008-07-11 | 2012-06-26 | Tyco Healthcare Group Lp | Functionalized inclusion complexes as crosslinkers |
DE102008040787A1 (en) | 2008-07-28 | 2010-02-04 | Biotronik Vi Patent Ag | Biocorrodible implant with a coating containing a hydrogel |
US8133436B2 (en) | 2008-08-05 | 2012-03-13 | Howmedica Osteonics Corp. | Polyethylene cross-linked with an anthocyanin |
US8246876B2 (en) | 2008-08-18 | 2012-08-21 | Cook Medical Technologies Llc | Embolization particles and method for making same |
US20100092533A1 (en) | 2008-10-15 | 2010-04-15 | Joshua Stopek | Bioabsorbable Surgical Composition |
EP2344556A1 (en) | 2008-10-22 | 2011-07-20 | Surmodics Inc. | Swellable biodegradable polymeric matrices and methods |
WO2010114633A1 (en) | 2009-04-03 | 2010-10-07 | Biomerix Corporation | At least partially resorbable reticulated elastomeric matrix elements and methods of making same |
WO2010123946A2 (en) | 2009-04-20 | 2010-10-28 | Allergan, Inc. | Silk fibroin hydrogels and uses thereof |
CN102713612B (en) | 2009-07-02 | 2016-10-05 | 斯隆-凯特林癌症研究院 | Fluorescent nano particle based on silica |
EP2451488A2 (en) | 2009-07-07 | 2012-05-16 | Bartling, Sönke | Multimodal visible polymer embolization material |
US20110202016A1 (en) | 2009-08-24 | 2011-08-18 | Arsenal Medical, Inc. | Systems and methods relating to polymer foams |
KR101103423B1 (en) | 2009-09-04 | 2012-01-06 | 아주대학교산학협력단 | In situ forming hydrogel for tissue adhesives and biomedical use thereof |
WO2011038291A1 (en) | 2009-09-24 | 2011-03-31 | Microvention, Inc. | Injectable hydrogel filaments for biomedical uses |
US20110093057A1 (en) | 2009-10-16 | 2011-04-21 | Confluent Surgical, Inc. | Mitigating Thrombus Formation On Medical Devices By Influencing pH Microenvironment Near The Surface |
AU2010313530B2 (en) | 2009-10-26 | 2015-12-17 | Microvention, Inc. | Embolization device constructed from expansile polymer |
WO2011057133A1 (en) | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Fragmented hydrogels |
JP5864429B2 (en) | 2009-11-09 | 2016-02-17 | スポットライト テクノロジー パートナーズ エルエルシーSpotlight Technology Partners Llc | Crosslinked hydrogel composition, method of forming hydrogel composition, and kit |
EP2506859B1 (en) | 2009-12-04 | 2016-05-04 | Magle AB | Microspheres of hydrolysed starch with endogenous, charged ligands |
EP2351779B1 (en) | 2010-01-27 | 2019-04-24 | Biosphere Medical, Inc. | Microspheres and method of making the microspheres |
EP2365009A1 (en) | 2010-03-10 | 2011-09-14 | Universite Claude Bernard Lyon 1 (UCBL) | Radiopaque, non-biodegradable, water-insoluble iodinated benzyl ethers of poly(vinyl alcohol), preparation method thereof, injectable embolizing compositions containing thereof and use thereof |
US9074095B2 (en) | 2010-06-03 | 2015-07-07 | Technology Innovation Momentum Fund (Israel) Limited Partnership | Malleable hydrogel hybrids made of self-assembled peptides and biocompatible polymers and uses thereof |
CN102107025B (en) | 2010-08-27 | 2014-05-21 | 上海微创医疗器械(集团)有限公司 | Embolic material composite and preparation method thereof |
KR101961961B1 (en) | 2010-09-21 | 2019-03-25 | 크리스탈 딜리버리 비.브이. | Tunable, biodegradable linker molecules for transient conjugation of components in drug delivery systems, and drug delivery systems prepared therewith |
US20120164100A1 (en) | 2010-11-02 | 2012-06-28 | Ren-Ke Li | Temperature sensitive hydrogel and block copolymers |
EP2683750B1 (en) | 2011-03-09 | 2017-04-19 | Occlugel | Implantable swellable bio-resorbable polymer |
US9456823B2 (en) | 2011-04-18 | 2016-10-04 | Terumo Corporation | Embolic devices |
CN102266591A (en) | 2011-06-17 | 2011-12-07 | 微创医疗器械(上海)有限公司 | Novel liquid embolic material based on collagen and preparation method thereof |
EP2744575A2 (en) | 2011-08-19 | 2014-06-25 | Pioneer Surgical Technology, Inc. | Injectable fillers for aesthetic medical enhancement and for therapeutic applications |
US9295761B2 (en) | 2011-10-13 | 2016-03-29 | Rowan University | Self-assembling biomimetic hydrogels having bioadhesive properties |
US9011884B2 (en) | 2012-04-18 | 2015-04-21 | Microvention, Inc. | Embolic devices |
US9662119B2 (en) | 2013-03-13 | 2017-05-30 | Lawrence Livermore National Security, Llc | Shape-memory polymer foam device for treating aneurysms |
US10328095B2 (en) | 2013-03-15 | 2019-06-25 | Covidien Lp | Resorbable oxidized cellulose embolization microspheres |
US10124090B2 (en) | 2014-04-03 | 2018-11-13 | Terumo Corporation | Embolic devices |
CN110433326A (en) | 2014-04-29 | 2019-11-12 | 微仙美国有限公司 | Polymer comprising activating agent |
WO2015167751A1 (en) | 2014-04-29 | 2015-11-05 | Microvention, Inc. | Polymers |
WO2016201250A1 (en) | 2015-06-11 | 2016-12-15 | Microvention, Inc. | Expansile device for implantation |
-
2008
- 2008-12-19 US US12/340,544 patent/US8470035B2/en active Active
- 2008-12-19 AU AU2008345590A patent/AU2008345590B2/en active Active
- 2008-12-19 CA CA2709379A patent/CA2709379C/en active Active
- 2008-12-19 JP JP2010539913A patent/JP5698537B2/en active Active
- 2008-12-19 EP EP10174867.1A patent/EP2266639B1/en active Active
- 2008-12-19 BR BRPI0821070A patent/BRPI0821070B1/en active IP Right Grant
- 2008-12-19 EP EP08867736.4A patent/EP2231215B1/en active Active
- 2008-12-19 WO PCT/US2008/087846 patent/WO2009086208A2/en active Application Filing
- 2008-12-19 KR KR1020107015323A patent/KR101567111B1/en active IP Right Grant
- 2008-12-19 CN CN2008801220567A patent/CN101903051B/en active Active
-
2013
- 2013-05-21 US US13/899,357 patent/US9486221B2/en active Active
-
2016
- 2016-09-21 US US15/272,305 patent/US10194915B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
EP2266639B1 (en) | 2016-10-05 |
KR101567111B1 (en) | 2015-11-06 |
BRPI0821070A2 (en) | 2015-06-16 |
KR20100105663A (en) | 2010-09-29 |
US20090164013A1 (en) | 2009-06-25 |
EP2266639A1 (en) | 2010-12-29 |
JP5698537B2 (en) | 2015-04-08 |
CN101903051A (en) | 2010-12-01 |
US8470035B2 (en) | 2013-06-25 |
US10194915B2 (en) | 2019-02-05 |
US9486221B2 (en) | 2016-11-08 |
CA2709379A1 (en) | 2009-07-09 |
EP2231215B1 (en) | 2019-01-30 |
AU2008345590A1 (en) | 2009-07-09 |
BRPI0821070B1 (en) | 2018-10-23 |
JP2011507637A (en) | 2011-03-10 |
WO2009086208A3 (en) | 2010-04-01 |
US20130253087A1 (en) | 2013-09-26 |
CN101903051B (en) | 2013-07-31 |
AU2008345590B2 (en) | 2014-10-30 |
WO2009086208A2 (en) | 2009-07-09 |
US20170007264A1 (en) | 2017-01-12 |
EP2231215A2 (en) | 2010-09-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10194915B2 (en) | Implantation devices including hydrogel filaments | |
US10232089B2 (en) | Embolic devices | |
US20220039802A1 (en) | Embolization Device Constructed From Expansile Polymer | |
US9381278B2 (en) | Embolic devices | |
AU2010298026B2 (en) | Injectable hydrogel filaments for biomedical uses | |
WO2015153996A1 (en) | Embolic devices |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |
Effective date: 20131024 |